慢性应激及去交感神经对大鼠前列腺的影响
|
摘要
研究背景与目的:人类和大鼠的前列腺,均接受两种自主神经纤维的支配,即来自腹下神经与盆神经的交感神经与副交感神经,分布于前列腺的间质平滑肌和腺上皮。绝大多数交感神经的节后纤维为肾上腺素能神经,副交感神经节后纤维为胆碱能神经,一般认为前列腺的间质平滑肌主要接受肾上腺素能神经支配,而上皮组织主要接受胆碱能神经支配。交感神经纤维末梢分泌神经递质为去甲肾上腺素,对前列腺间质细胞的分化及血管、平滑肌的收缩具有重要作用。前列腺内的副交感神经刺激腺泡的分泌,而交感神经则促使前列腺液排入尿道内。交感神经和副交感神经调节正常前列腺的发育和生长。
当机体受到各种强烈刺激,如缺氧、创伤、手术、饥饿、疼痛、寒冷及精神紧张和焦虑不安等,机体就会出现以交感神经系统(SNS)兴奋,儿茶酚胺分泌增多和下丘脑-垂体-肾上腺皮质轴(HPA)分泌增多为主的一系列神经内分泌反应,以适应强烈的刺激,提高机体抗病的能力。一般将能引起促肾上腺皮质激素与糖皮质激素分泌增加的各种刺激,称为应激刺激,由应激刺激引起的机体反应称为应激反应。在这一反应中,除了促肾上腺皮质激素、糖皮质激素分泌增加外,儿茶酚胺分泌也增加。
前列腺炎是男性泌尿生殖系统常见疾病,其中慢性前列腺炎(CP)/慢性骨盆疼痛综合症(CPPS)虽占前列腺炎的90-95%,但病因不明。虽然心理应激被认为是其中的致病因素,但潜在的机制没有被具体的阐明。Gatenbeck L等报道短期的标准化的应激刺激能够诱导出大鼠前列腺的无菌性炎症和血流灌注的减少,并同时也在实验中测得儿茶酚胺的增高,认为这种炎症的发生可能是血流减少的结果,但对长期的应激刺激对前列腺的作用没有进行研究。Rosenzweig等在试验中给大鼠每日注射肾上腺素类神经递质苯肾上腺素后,短期内能够诱导大鼠前列腺的炎性病变,并在第7天观察到前列腺内上皮瘤样增生。这些都提示了交感神经在前列腺疾病中起着重要的作用。
尽管前列腺增生的发生一直被认为是老龄和雄激素功能存在的结果,对前列腺增生病因的认识仍不清楚。对高血压人群的良性前列腺增生(BPH)发病率的调查结果以及在遗传性高血压大鼠中观察到自发性前列腺组织增生病变均提示前列腺病变与高血压之间有着相关性,而高血压的发生正是和交感神经末梢神经递质的过量释放密切相关。最近的资料显示在BPH患者中,标准化实验应激引起的交感神经过度活动与前列腺增生疾病的主、客观的评价参数相关,表明应激状态和前列腺疾病的发生和进展之间有着某种相关性。
最近越来越多的研究重视代谢综合征和它的主要内分泌紊乱—高胰岛素血症在前列腺增生发病中的作用,代谢综合征和高胰岛血症的患者在应激负荷时有着高的SNS和HPA轴的反应性,而短期或长期的应激均能引起血胰岛素水平的增高。越来越多的数据显示交感神经活性增高也可能是前列腺增生及伴随的下尿路症状(LUTS)产生的独立的致病因素。去除交感神经能够引起大鼠前列腺腹侧叶重量、DNA及蛋白含量的减少。交感神经的功能异常对前列腺有促有丝分裂的作用。临床应用α受体阻滞剂可以通过恢复自主神经的平衡,并直接作用于前列腺,影响其生长和增大。
大鼠的盆神经节接受两种不同的神经输入,其节后神经支配盆腔脏器,即腹下神经(交感神经)和盆神经(副交感神经)。腹下神经和盆神经的纤维广泛分布到前列腺,调节前列腺的生长、发育和功能。Gosling于1983年通过组织化学染色的方法发现,胆碱能的神经纤维支配上皮细胞、包膜,以及间质的一些平滑肌细胞,而肾上腺素能神经主要支配包膜和间质的平滑肌细胞。两种不同神经在前列腺发挥不同的功能,Wang和Bruschini等研究发现拟交感神经药通过收缩平滑肌促使前列腺分泌,而拟副交感神经药通过刺激上皮细胞分泌的某种机制引起前列腺液的产生。由此从功能上判断得到的结论便是:交感神经主要支配间质,副交感神经支配上皮。同其他实验动物盆神经丛有许多散在分布且相互间联系的盆神经节组成不同,大鼠的盆神经节有单一的主要的神经节(Maj,P.G)组成,且接受独立的交感和副交感神经的输入,这就为研究交感神经对前列腺的影响提供了理想的模型。大鼠的前列腺间质的血管和平滑肌表达多种α受体,接受交感神经的支配,调节间质的生长、发育及血管平滑肌收缩,并通过间质—上皮细胞间的相互作用调节腺上皮的生长和分化,间质—上皮相互作用同样在前列腺增生发病中发挥作用。
我们推测应激可以通过交感神经的过度活动,进而影响前列腺的功能,导致疾病的产生,阻断交感神经将抑制前列腺疾病的发生。本研究应用束缚浸水实验制造大鼠心理应激模型,观察慢性应激及阻断交感神经对大鼠前列腺的影响,包括血流、重量、前列腺液分泌、组织病理及神经生长因子(NGF)表达的改变,探讨交感神经系统在前列腺疾病中发挥的作用。
材料与方法
3月龄SPF级雄性wistar大鼠购于山东大学、山东中医药大学实验动物中心,共32只,每4只一笼。大鼠饲养于山东大学实验动物中心,将大鼠置于昼夜节律光照条件下,自由进食进水,室温在18-22℃,饲养一周以适应环境,每日触摸1次,每次约2分钟,使动物适应实验人员的操作。
1.应激方法:
大鼠束缚浸水实验:动物随机分成四组:A、正常对照组,B、应激组,C、去交感神经组,D、应激+去交感神经组,每组8只。
应激过程:B、D组大鼠每日行束缚浸水1小时,连续14天。对照组不接受任何刺激,自由摄食饮水。大鼠在束缚实验期间禁水、禁食。束缚浸水实验:把实验大鼠用传统方法束缚后放置在23℃温水中,水面和大鼠剑突平齐。
2.化学性去交感神经:B、D组于应激第1、8天给予六羟多巴胺50mg/kg尾静脉注射。
3.麻醉方法:10%水合氯醛,每0.3ml对应100g大鼠,腹腔注射。
4.观测指标:
(1)前列腺腹侧叶血流测定
应用Periflux system 5000多普勒超声测定大鼠腹侧叶血流灌注情况。每只大鼠经麻醉后,仰卧,下腹部切口。仔细暴露前列腺的腹侧叶,将探针头轻轻放在上面。静止的放置30s以稳定测量血流值并记录。随机选取器官表面3点测量,获得均值。同法测定肾脏的血流。
(2)采血测定血皮质醇、肾上腺素及去甲肾上腺素水平
动物处死前,使用预冷注射器从大鼠颈静脉采血7ml,加入预先干燥的肝素管,-4℃3000r/min低温离心15分钟分离血浆。吸取血浆加入预冷试管中储存于-30℃,30d内应用高效液相色谱法测定血儿茶酚胺水平,放免法测定皮质醇浓度。
(3)前列腺标本处理:
每组中6只大鼠:暴露前列腺叶,右侧的腹侧叶(VP)、侧叶(LP)、背侧叶(DP)被分离,每2只大鼠右侧前列腺的相同叶放在一起(每叶有3个集合的标本)用来提取分泌物。解剖左侧的VP、LP、DP,并固定于10%的福尔马林中预备组织学检查。
另2只大鼠:每只取成对的VP、LP、DP,称重,用来准备分泌物。
分泌物的提取是将分离的前列腺叶用镊子撕开,在50ml的聚丙烯离心管内不锈钢的滤网上低速离心:150g×3min 4℃。移走带有组织的滤网,离心管中收集的液体再次离心:960g×10min 4℃以去除细胞。收集上清,称容,并做为前列腺分泌物冷冻于粉状干冰中。滤网上的组织称重并冷冻于-70℃。
(4)前列腺组织学
大鼠左侧前列腺三侧叶均切片,切片厚度4μm,每个标本连续切片2片,1片行苏木素—伊红染色,1片做NGF免疫组化染色。Olympus BX51倒置荧光显微镜观察组织切片,Olympus DP71图象采集系统在相同光透量情况下采集图像。对每个标本HE染色切片进行病理学检查(由病理科医生协助完成),应用美国Image Pro-Plus图像分析系统对组化切片进行图像分析,测得每个切片阳性细胞的平均光密度值。
5.统计方法
统计方法以双因素析因设计资料的方差分析检验组间差异显著性,统计处理软件为SPSS13.0,实验数据计算平均值和标准差(X±SD),P＜0.05认为差异有显著性意义。
结果
一、慢性应激对大鼠前列腺腹侧叶血流灌注的影响
1.同对照组相比,慢性应激使腹侧叶前列腺和肾脏的血流灌注量分别减少了大约15%(P＜0.05)和18%,对两者血流比值无明显影响。
2.同对照组相比,去除外周交感神经组大鼠前列腺血流增加了1倍(P＜0.01),应激并去除交感神经组大鼠前列腺血流增加了1.4倍(P＜0.05)。两组前列腺血流均比单纯应激组明显增高(P＜0.05),前列腺/肾脏血流比值较对照组及单纯应激组明显增高(P＜0.05)。
二、慢性应激对大鼠前列腺各叶重量及分泌的影响
1.与对照组相比,慢性应激组大鼠前列腺腹侧叶重量显著降低(P＜0.01),应激并去除交感神经组腹侧叶重量亦降低(P＜0.05),两组前列腺液分泌量均降低(P＜0.05)。
2.去除交感神经组大鼠前列腺腹侧叶重量降低(P＜0.01),前列腺分泌同对照组无明显差异。
3.慢性应激组及去神经组大鼠侧叶重量增加(P＜0.05),前列腺液分泌量同对照组相比无明显差异。
4.去除交感神经组背侧叶重量及前列腺液分泌均明显增加(P＜0.05)。
三、慢性应激对大鼠血浆皮质醇和儿茶酚胺(肾上腺素及去甲肾上腺素)水平的影响
1.慢性应激组及去神经组大鼠血浆皮质醇浓度较对照组明显增加(P＜0.05),去神经后应激较单纯应激组皮质醇水平下降。
2.慢性应激及去除交感神经后大鼠血肾上腺素水平较对照组均降低(P＜0.05),两者间存在协同作用(P＜0.05)。
3.各组中血去甲肾上腺素水平无明显差异。
四、慢性应激对大鼠前列腺组织学的影响
1.对照组大鼠,每叶的前列腺腺泡呈圆形或椭圆形,由单层的高柱状上皮组成。慢性应激组腹侧叶上皮呈增生性改变,表现为上皮向腺泡内绒毛样生长、小结形成、细胞重叠成多层和极性的丧失,腺泡形态呈波形;而侧叶、背侧叶几乎未受影响。
2.化学性去除交感神经导致前列腺腺泡的扩张。
3.应激并去神经组大鼠,腹侧叶腺泡可见扩张,没有观察到上皮增生的改变。所有三叶均可见上皮的萎缩和发育不良。
五、慢性应激对神经生长因子表达的影响
1.对照组大鼠前列腺上皮胞浆内可见神经生长因子的表达,间质未见明显NGF的表达。
2.慢性应激后腹侧叶腺上皮神经生长因子表达增高(P＜0.01),侧叶表达减少(P＜0.05),背侧叶无明显变化。
3.去除神经后腹侧叶(P＜0.01)及侧叶神经生长因子表达均明显减少(P＜0.05),背侧叶无明显变化。
4.去神经后应激组腹侧叶及侧叶NGF表达较单纯去神经组高,去神经及应激两者间存在交互作用(P＜0.05)。
结论
1.慢性应激能够引起大鼠腹侧前列腺叶血流灌注、重量及前列腺液分泌量的减少,血浆皮质醇升高。
2.慢性应激可以使大鼠前列腺腹侧叶上皮呈增生样改变,而侧叶、背侧叶基本不受影响。
3.去除交感神经导致前列腺腺泡的扩张,同时给予应激时腹侧叶上皮未见增生改变。交感神经的过度活动参与前列腺疾病的发病。
4.神经生长因子表达于大鼠前列腺上皮细胞,应激后腹侧叶NGF表达升高,去神经后可见显著降低,NGF水平变化参与应激及去神经引起的增生和萎缩改变。
Background and Objective:
The prostate gland in both man and rat is richly innervated with adrenergic and cholinergic nerve fibers. It receives both sympathetic and parasympathetic neural input. Sympathetic input is supplied by the hypogastric nerve, while parasympathetic input is furnished by the pelvic nerve. Adrenergic fibers functionally innervate the stroma, and cholinergic ones innervate the epithelium. The potential involvement of the sympathetic nervous system in the pathogenesis of benign prostatic hyperplasia has recently attracted scientific interest. Experimental denervation of the prostate induces atrophic changes of the acini as well as a decrease in their secretory activity. Moreover,α-adrenergic antagonists have been used for the treatment of BPH for many years.
Stress can effect the function of almost all organ systems, most likely due to production and release of several humoral factors. The sympathetic nervous system and hypothalamic-pituitary-adrenal axis have been known to reactive to psychological factors such as stress. Growing data suggests that stress conditions could be associated with the development or aggravation of prostatic disease including prostatis and benign prostatic hyperplasia. The present study aims to investigate the influence of chronic stress and blockade of sympathetic nerve on rat prostate.
Materials and Methods:
Male Wistar rats (90 days of age) purchased from Animal Center of Shandong University were used. We used the model of Vaalasti A et al. of chemical sympathectomy with 6-hydroxydopamine (6-OHDA) on the ventral prostate of the rat and restraint water-immersion stress (WIRS) on rats. The rats were divided into four groups of eight rats each as follows. A: an untreated control group. B: In this group rats were under WIRS 1h/d for 2 weeks. C: On the day 1 and 8, 6-OHDA was administered with a dose of 50mg/kg i.v. D: WIRS daily plus 6-OHDA on day 1 and 8 as above. The experiment was terminated at 14 days. Blood flow of ventral prostate, plasma catecholamine and cortisol were measured. The weight and secretions of dissected prostate lobes were measured and histology was performed by hematoxylin and eosin stain. Immunohistochemical staining of nerve growth factor (NGF) was also investigated.
Results:
After 14 days' stress, the blood flow of ventral prostate decreased and plasma cortisol increased. The level of catecholamine in rat blood had no significant change after chronic stress or denervation of peripheral sympathetic nerve. Chronic stress resulted in loses of tissue weight and secretions of the ventral lobes of the rat prostatic complex, while tissue weight of ventral prostate was also reduced in 6-OHDA treated rats. In the WIRS group, the apparent proliferation of epithelium of ventral lobes were observed and dorsolateral ones were almost unaffected. On the other hand, the hyperplasia changes were not seen after the chemical sympathectomy had been done during stress.
NGF immunoreactive protein localized to the columnar secretory epithelium lines of prostate tissue. Stress increased NGF expression in ventral lobes. Denervation led to significant decreation of NGF level in ventral and lateral lobes. Stress after denervation increased expression of NGF.
Conclusions:
Chronic stress may induce epithelial proliferation of ventral prostate in rats, the overactivity of sympathetic nervous system is involved in the pathogenesis of prostatic disease. NGF has a mitogenic effect on prostate. It is involved in the hyperplasia and atrophy in prostate of male rat in response to chronic stress and denervation.
当机体受到各种强烈刺激,如缺氧、创伤、手术、饥饿、疼痛、寒冷及精神紧张和焦虑不安等,机体就会出现以交感神经系统(SNS)兴奋,儿茶酚胺分泌增多和下丘脑-垂体-肾上腺皮质轴(HPA)分泌增多为主的一系列神经内分泌反应,以适应强烈的刺激,提高机体抗病的能力。一般将能引起促肾上腺皮质激素与糖皮质激素分泌增加的各种刺激,称为应激刺激,由应激刺激引起的机体反应称为应激反应。在这一反应中,除了促肾上腺皮质激素、糖皮质激素分泌增加外,儿茶酚胺分泌也增加。
前列腺炎是男性泌尿生殖系统常见疾病,其中慢性前列腺炎(CP)/慢性骨盆疼痛综合症(CPPS)虽占前列腺炎的90-95%,但病因不明。虽然心理应激被认为是其中的致病因素,但潜在的机制没有被具体的阐明。Gatenbeck L等报道短期的标准化的应激刺激能够诱导出大鼠前列腺的无菌性炎症和血流灌注的减少,并同时也在实验中测得儿茶酚胺的增高,认为这种炎症的发生可能是血流减少的结果,但对长期的应激刺激对前列腺的作用没有进行研究。Rosenzweig等在试验中给大鼠每日注射肾上腺素类神经递质苯肾上腺素后,短期内能够诱导大鼠前列腺的炎性病变,并在第7天观察到前列腺内上皮瘤样增生。这些都提示了交感神经在前列腺疾病中起着重要的作用。
尽管前列腺增生的发生一直被认为是老龄和雄激素功能存在的结果,对前列腺增生病因的认识仍不清楚。对高血压人群的良性前列腺增生(BPH)发病率的调查结果以及在遗传性高血压大鼠中观察到自发性前列腺组织增生病变均提示前列腺病变与高血压之间有着相关性,而高血压的发生正是和交感神经末梢神经递质的过量释放密切相关。最近的资料显示在BPH患者中,标准化实验应激引起的交感神经过度活动与前列腺增生疾病的主、客观的评价参数相关,表明应激状态和前列腺疾病的发生和进展之间有着某种相关性。
最近越来越多的研究重视代谢综合征和它的主要内分泌紊乱—高胰岛素血症在前列腺增生发病中的作用,代谢综合征和高胰岛血症的患者在应激负荷时有着高的SNS和HPA轴的反应性,而短期或长期的应激均能引起血胰岛素水平的增高。越来越多的数据显示交感神经活性增高也可能是前列腺增生及伴随的下尿路症状(LUTS)产生的独立的致病因素。去除交感神经能够引起大鼠前列腺腹侧叶重量、DNA及蛋白含量的减少。交感神经的功能异常对前列腺有促有丝分裂的作用。临床应用α受体阻滞剂可以通过恢复自主神经的平衡,并直接作用于前列腺,影响其生长和增大。
大鼠的盆神经节接受两种不同的神经输入,其节后神经支配盆腔脏器,即腹下神经(交感神经)和盆神经(副交感神经)。腹下神经和盆神经的纤维广泛分布到前列腺,调节前列腺的生长、发育和功能。Gosling于1983年通过组织化学染色的方法发现,胆碱能的神经纤维支配上皮细胞、包膜,以及间质的一些平滑肌细胞,而肾上腺素能神经主要支配包膜和间质的平滑肌细胞。两种不同神经在前列腺发挥不同的功能,Wang和Bruschini等研究发现拟交感神经药通过收缩平滑肌促使前列腺分泌,而拟副交感神经药通过刺激上皮细胞分泌的某种机制引起前列腺液的产生。由此从功能上判断得到的结论便是:交感神经主要支配间质,副交感神经支配上皮。同其他实验动物盆神经丛有许多散在分布且相互间联系的盆神经节组成不同,大鼠的盆神经节有单一的主要的神经节(Maj,P.G)组成,且接受独立的交感和副交感神经的输入,这就为研究交感神经对前列腺的影响提供了理想的模型。大鼠的前列腺间质的血管和平滑肌表达多种α受体,接受交感神经的支配,调节间质的生长、发育及血管平滑肌收缩,并通过间质—上皮细胞间的相互作用调节腺上皮的生长和分化,间质—上皮相互作用同样在前列腺增生发病中发挥作用。
我们推测应激可以通过交感神经的过度活动,进而影响前列腺的功能,导致疾病的产生,阻断交感神经将抑制前列腺疾病的发生。本研究应用束缚浸水实验制造大鼠心理应激模型,观察慢性应激及阻断交感神经对大鼠前列腺的影响,包括血流、重量、前列腺液分泌、组织病理及神经生长因子(NGF)表达的改变,探讨交感神经系统在前列腺疾病中发挥的作用。
材料与方法
3月龄SPF级雄性wistar大鼠购于山东大学、山东中医药大学实验动物中心,共32只,每4只一笼。大鼠饲养于山东大学实验动物中心,将大鼠置于昼夜节律光照条件下,自由进食进水,室温在18-22℃,饲养一周以适应环境,每日触摸1次,每次约2分钟,使动物适应实验人员的操作。
1.应激方法:
大鼠束缚浸水实验:动物随机分成四组:A、正常对照组,B、应激组,C、去交感神经组,D、应激+去交感神经组,每组8只。
应激过程:B、D组大鼠每日行束缚浸水1小时,连续14天。对照组不接受任何刺激,自由摄食饮水。大鼠在束缚实验期间禁水、禁食。束缚浸水实验:把实验大鼠用传统方法束缚后放置在23℃温水中,水面和大鼠剑突平齐。
2.化学性去交感神经:B、D组于应激第1、8天给予六羟多巴胺50mg/kg尾静脉注射。
3.麻醉方法:10%水合氯醛,每0.3ml对应100g大鼠,腹腔注射。
4.观测指标:
(1)前列腺腹侧叶血流测定
应用Periflux system 5000多普勒超声测定大鼠腹侧叶血流灌注情况。每只大鼠经麻醉后,仰卧,下腹部切口。仔细暴露前列腺的腹侧叶,将探针头轻轻放在上面。静止的放置30s以稳定测量血流值并记录。随机选取器官表面3点测量,获得均值。同法测定肾脏的血流。
(2)采血测定血皮质醇、肾上腺素及去甲肾上腺素水平
动物处死前,使用预冷注射器从大鼠颈静脉采血7ml,加入预先干燥的肝素管,-4℃3000r/min低温离心15分钟分离血浆。吸取血浆加入预冷试管中储存于-30℃,30d内应用高效液相色谱法测定血儿茶酚胺水平,放免法测定皮质醇浓度。
(3)前列腺标本处理:
每组中6只大鼠:暴露前列腺叶,右侧的腹侧叶(VP)、侧叶(LP)、背侧叶(DP)被分离,每2只大鼠右侧前列腺的相同叶放在一起(每叶有3个集合的标本)用来提取分泌物。解剖左侧的VP、LP、DP,并固定于10%的福尔马林中预备组织学检查。
另2只大鼠:每只取成对的VP、LP、DP,称重,用来准备分泌物。
分泌物的提取是将分离的前列腺叶用镊子撕开,在50ml的聚丙烯离心管内不锈钢的滤网上低速离心:150g×3min 4℃。移走带有组织的滤网,离心管中收集的液体再次离心:960g×10min 4℃以去除细胞。收集上清,称容,并做为前列腺分泌物冷冻于粉状干冰中。滤网上的组织称重并冷冻于-70℃。
(4)前列腺组织学
大鼠左侧前列腺三侧叶均切片,切片厚度4μm,每个标本连续切片2片,1片行苏木素—伊红染色,1片做NGF免疫组化染色。Olympus BX51倒置荧光显微镜观察组织切片,Olympus DP71图象采集系统在相同光透量情况下采集图像。对每个标本HE染色切片进行病理学检查(由病理科医生协助完成),应用美国Image Pro-Plus图像分析系统对组化切片进行图像分析,测得每个切片阳性细胞的平均光密度值。
5.统计方法
统计方法以双因素析因设计资料的方差分析检验组间差异显著性,统计处理软件为SPSS13.0,实验数据计算平均值和标准差(X±SD),P＜0.05认为差异有显著性意义。
结果
一、慢性应激对大鼠前列腺腹侧叶血流灌注的影响
1.同对照组相比,慢性应激使腹侧叶前列腺和肾脏的血流灌注量分别减少了大约15%(P＜0.05)和18%,对两者血流比值无明显影响。
2.同对照组相比,去除外周交感神经组大鼠前列腺血流增加了1倍(P＜0.01),应激并去除交感神经组大鼠前列腺血流增加了1.4倍(P＜0.05)。两组前列腺血流均比单纯应激组明显增高(P＜0.05),前列腺/肾脏血流比值较对照组及单纯应激组明显增高(P＜0.05)。
二、慢性应激对大鼠前列腺各叶重量及分泌的影响
1.与对照组相比,慢性应激组大鼠前列腺腹侧叶重量显著降低(P＜0.01),应激并去除交感神经组腹侧叶重量亦降低(P＜0.05),两组前列腺液分泌量均降低(P＜0.05)。
2.去除交感神经组大鼠前列腺腹侧叶重量降低(P＜0.01),前列腺分泌同对照组无明显差异。
3.慢性应激组及去神经组大鼠侧叶重量增加(P＜0.05),前列腺液分泌量同对照组相比无明显差异。
4.去除交感神经组背侧叶重量及前列腺液分泌均明显增加(P＜0.05)。
三、慢性应激对大鼠血浆皮质醇和儿茶酚胺(肾上腺素及去甲肾上腺素)水平的影响
1.慢性应激组及去神经组大鼠血浆皮质醇浓度较对照组明显增加(P＜0.05),去神经后应激较单纯应激组皮质醇水平下降。
2.慢性应激及去除交感神经后大鼠血肾上腺素水平较对照组均降低(P＜0.05),两者间存在协同作用(P＜0.05)。
3.各组中血去甲肾上腺素水平无明显差异。
四、慢性应激对大鼠前列腺组织学的影响
1.对照组大鼠,每叶的前列腺腺泡呈圆形或椭圆形,由单层的高柱状上皮组成。慢性应激组腹侧叶上皮呈增生性改变,表现为上皮向腺泡内绒毛样生长、小结形成、细胞重叠成多层和极性的丧失,腺泡形态呈波形;而侧叶、背侧叶几乎未受影响。
2.化学性去除交感神经导致前列腺腺泡的扩张。
3.应激并去神经组大鼠,腹侧叶腺泡可见扩张,没有观察到上皮增生的改变。所有三叶均可见上皮的萎缩和发育不良。
五、慢性应激对神经生长因子表达的影响
1.对照组大鼠前列腺上皮胞浆内可见神经生长因子的表达,间质未见明显NGF的表达。
2.慢性应激后腹侧叶腺上皮神经生长因子表达增高(P＜0.01),侧叶表达减少(P＜0.05),背侧叶无明显变化。
3.去除神经后腹侧叶(P＜0.01)及侧叶神经生长因子表达均明显减少(P＜0.05),背侧叶无明显变化。
4.去神经后应激组腹侧叶及侧叶NGF表达较单纯去神经组高,去神经及应激两者间存在交互作用(P＜0.05)。
结论
1.慢性应激能够引起大鼠腹侧前列腺叶血流灌注、重量及前列腺液分泌量的减少,血浆皮质醇升高。
2.慢性应激可以使大鼠前列腺腹侧叶上皮呈增生样改变,而侧叶、背侧叶基本不受影响。
3.去除交感神经导致前列腺腺泡的扩张,同时给予应激时腹侧叶上皮未见增生改变。交感神经的过度活动参与前列腺疾病的发病。
4.神经生长因子表达于大鼠前列腺上皮细胞,应激后腹侧叶NGF表达升高,去神经后可见显著降低,NGF水平变化参与应激及去神经引起的增生和萎缩改变。
Background and Objective:
The prostate gland in both man and rat is richly innervated with adrenergic and cholinergic nerve fibers. It receives both sympathetic and parasympathetic neural input. Sympathetic input is supplied by the hypogastric nerve, while parasympathetic input is furnished by the pelvic nerve. Adrenergic fibers functionally innervate the stroma, and cholinergic ones innervate the epithelium. The potential involvement of the sympathetic nervous system in the pathogenesis of benign prostatic hyperplasia has recently attracted scientific interest. Experimental denervation of the prostate induces atrophic changes of the acini as well as a decrease in their secretory activity. Moreover,α-adrenergic antagonists have been used for the treatment of BPH for many years.
Stress can effect the function of almost all organ systems, most likely due to production and release of several humoral factors. The sympathetic nervous system and hypothalamic-pituitary-adrenal axis have been known to reactive to psychological factors such as stress. Growing data suggests that stress conditions could be associated with the development or aggravation of prostatic disease including prostatis and benign prostatic hyperplasia. The present study aims to investigate the influence of chronic stress and blockade of sympathetic nerve on rat prostate.
Materials and Methods:
Male Wistar rats (90 days of age) purchased from Animal Center of Shandong University were used. We used the model of Vaalasti A et al. of chemical sympathectomy with 6-hydroxydopamine (6-OHDA) on the ventral prostate of the rat and restraint water-immersion stress (WIRS) on rats. The rats were divided into four groups of eight rats each as follows. A: an untreated control group. B: In this group rats were under WIRS 1h/d for 2 weeks. C: On the day 1 and 8, 6-OHDA was administered with a dose of 50mg/kg i.v. D: WIRS daily plus 6-OHDA on day 1 and 8 as above. The experiment was terminated at 14 days. Blood flow of ventral prostate, plasma catecholamine and cortisol were measured. The weight and secretions of dissected prostate lobes were measured and histology was performed by hematoxylin and eosin stain. Immunohistochemical staining of nerve growth factor (NGF) was also investigated.
Results:
After 14 days' stress, the blood flow of ventral prostate decreased and plasma cortisol increased. The level of catecholamine in rat blood had no significant change after chronic stress or denervation of peripheral sympathetic nerve. Chronic stress resulted in loses of tissue weight and secretions of the ventral lobes of the rat prostatic complex, while tissue weight of ventral prostate was also reduced in 6-OHDA treated rats. In the WIRS group, the apparent proliferation of epithelium of ventral lobes were observed and dorsolateral ones were almost unaffected. On the other hand, the hyperplasia changes were not seen after the chemical sympathectomy had been done during stress.
NGF immunoreactive protein localized to the columnar secretory epithelium lines of prostate tissue. Stress increased NGF expression in ventral lobes. Denervation led to significant decreation of NGF level in ventral and lateral lobes. Stress after denervation increased expression of NGF.
Conclusions:
Chronic stress may induce epithelial proliferation of ventral prostate in rats, the overactivity of sympathetic nervous system is involved in the pathogenesis of prostatic disease. NGF has a mitogenic effect on prostate. It is involved in the hyperplasia and atrophy in prostate of male rat in response to chronic stress and denervation.
引文
1. Wei JT, Calhoun E, Jacobsen SJ. Urologic Diseases in America project: benign prostatic hyperplasia. J Urol 2005;173:1256-1261.
2. McVary KT, McKenna KE, Lee C. Prostate innervation. Prostate Suppl 1998;8:2-13.
3. Vaalasti A, Hervonen A. Autonomic innervation of the human prostate. Invest Urol 1980;17:293-297.
4. Purinton PT, Fletcher TF, Bradley WE. Gross and light microscopic features of the pelvic pleus in the rat. Anat Rec 1972;175:697-706.
5. Lepor H, Shapiro E, Bowsher RR, Henry DP: Determination of norepinephrine levels in the adult human prostate. J Urol 1990;144:1263-1266.
6. Tong YC, Hung YC, Lin SN, Cheng JT: The norepinephrine tissue concentration and neuropeptide Y immunoreactivity in genitourinary organs of the spontaneously hypertensive rat. J AutonNerv Syst 1996;56:215—218.
7. Hieble JP, Bylund DB, Clarke DE, Eikenburg DC, Langer SZ, Lefkowitz RJ, Minneman KP, Ruffolo RR: International union of pharmacology X. Recommendation for nomenclature of alpha1-adrenoceptors: consensus update. Pharmacol. Rev. 1995; 47: 267-70.
8. Marinese D, Patel R, Walden PD, et al. Mechanistic investigation of the adrenergic induction of ventral prostate hyperplasia in mice. Prostate 2003;54:230-237.
9. McVary KT, Razzaq A, Lee C, Rademaker A, McKenna KE. Growth of the rat prostate gland is facilitated by the autonomic nervous system. Biol Reprod 1994;51:99-107.
10. Jacobs SC, Story MT: Exocrine secretion of epidermal growth factor by the rat prostate: Effect of adrenergic agents, cholinergic agents and vasoactive intestinal peptide. Prostate 1988; 13:79-87.
11. Smith P, Rhodes NP, Beesley C, Ke Y, Foster CS. Prostatic stromal cell phenotype is diercetly modulated by norepinephrine. Urology 1998;51:663-670.
12. Kyprianou N, Litvak JP, Borkowski A, et al. Induction of prostate apoptosis by doxazosin in benign prostatic hyperplasia. J Urol 1998;159:1810-1815.
13. Kyprianou N. Doxazosin and terazosin suppress prostate growth by inducing apoptosis: clinical significance. J Urol 2003;169:1520-1525.
14. Golomb E, Kruglikova A, Dvir D, et al. Induction of atypical prostatic hyperplasia in rats by sympathomimetic stimulation. Prostate 1998;34:214-221.
15. GassR. Benign prostatic hyperplasia: the opposite effects of alcohol and coffee intake. BJU Int 2002;90:649-654.
16. Mc Vary KT, Rademaker A, Lloyd GL, et al. Autonomic nervous system overactivity in men with lower urinary tract symptoms secondary to benign prostatic hyperplasia. J Urol 2005;174:1327-1333.
17. Ullrich PM, Lutgendorf SK, Kreder KJ: Physiologic reactivity to a laboratory stress task among men with benign prostatic hyperplasia. Urology 2007;70:487-491.
18. Meigs JB, Mohr B, Barry MJ, Collins MM, McKinlay JB: Risk factors for clinical benign prostatic hyperplasia in a community-based population of healthy aging men. J Clin Epidemiol 2001;54:935-944.
19. Golomb E, Rosenzweig N, Eilam R, et al. Spontaneous hyperplasia of the ventral lobe of the prostate in aging genetically hypertensive rats. J Androl 2000,21:58-64.
20. Clemow DB, Spitsbergen JM, McCarty R, et al. Altered NGF regulation may link a genetic predisposition for hypertension with hyperactive voiding. J Urol 1999;161:1372-1377.
21. Snider WD. Functions of the neurotrophins during nervous system development: what the knockouts are teaching us. Cell 1994;77:627-638
22. Paul AB, Grant ES, Habib FK. The expression and localization of P-nerve growth factor (P-NGF) in benign and malignant human prostate tissue: relationship to neuroendocrine differentiation. Br J Cancer 1996;74:1990-1996
23. Dalai R, Djakiew D. Molecular characterization of neurotrophin expression and the corresponding tropomyosin receptor kinases (trks) in epithelial and stromal cells of the human prostate. Mole Cell Endocrinol 1997;134:15-22.
24. Li C, Watanabe G, Weng Q, et al. Expression of nerve growth factor (NGF), and its receptors TrkA and p75 in the reproductive organs of the adult male rats. Zoolog Sci 2005;22:933-937.
25. Eyres HM. Nervous retention of urine. BMJ 1912;1:484-487.
26. Gosling JA. Autonomic innervation of the prostate;in Hinman F(ed):Benign Prostatic Hypertrophy. New York, Springer-Verlag,1983,pp349-360.
27. Wang JM, McKenna KE, Lee C. Determination of prostatic secretion in rats: effect of neurotransmitters and testosterone. The Prostate 1991; 18:289-301.
28. Bruschini H, Schmidt RA, Tanagho EA. Neurologic control of prostatic secretion in the dog. Invest Urol 1978; 15:288-290.
29. Keast JR, Luckensmeyer GB, Schemann M. All pelvic neurons in male rats contain synthetic enzymes for either noradrenaline or acetylcholine. Neurosci Lett 1995; 196:209-212.
30. Hedlund P. Nitric oxide/cGMP-mediated eVects in the out-flow region of the lower urinary tract - is there a basis for pharmacological targeting of cGMP? World J Urol 2005;23:362-367.
31. Andersson KE. LUTS treatment: future treatment options. Neurourol Urodyn 2007;26:928-933.
32. Michel MC, Vrydag W. Alphal-, alpha2- and beta-adrenoceptors in the urinary bladder, urethra and prostate. Br J Pharmacol 2006;147:88-119.
33. Hawrylyshyn KA, Michelotti GA, Coge F, et al. Update on human alpha1-adrenoceptor subtype signaling and genomic organization. Trends Pharmacol Sci 2004;25:449-455.
34. Price DT, Lefkowitz RJ, Caron MG, et al. Localization of mRNA for three distinct alpha 1-adrenergic receptor subtypes in human tissues: implications for human alpha-adrenergic physiology. Mol Pharmacol 1994; 45: 171-175.
35. Lepor H, Zhang W, Kobayashi S, et al. A comparison of the binding and functional properties of alpha-1 adrenoceptors and area density of smooth muscle in the human, canine and rat prostate. J Pharmacol Exp Ther 1994; 270:722-727.
36. Shapiro E, Becich MJ, Hartanto V. The relative proportion of stromal and epithelial hyperplasia is related to the development of symptomatic benign prostatic hyperplasia. J Urol 1992;147:1293-1297.
37. Roehrborn CG, Schwinn DA. al-Adrenergic receptors and their inhibitors in lower urinary tract symptoms and benign prostatic hyperplasia. J Urol 2004;171:1029-1035.
38.Kojima Y, Sasaki S, Shinoura H, et al. Change of expression levels of alpha1-adrenoceptor subtypes by administration of alpha1d-adrenoceptor-subtype-selective antagonist naftopidil in benign prostate hyperplasia patients. Prostate 2007;67:1285-1292.
39. Smith M, Schambra U, Wilson K, et al. Alphal-adrenergic receptors in human spinal cored: specific localized expression of mRNA encoding alphal-adrenergic receptor subtypes at four distinct levels. Mol Brain Res 1999;63:254-261.
40. Bouchelouche K, Andersen L, Alvarez S, et al. Increased contractile response to phenylephrine in detrusor of patients with bladder outlet obstruction: effect of the alphal A and alphal D-adrenergic receptor antagonist tamsulosin. J Urol 2005;173:657-661.
41. Souverein PC, Van Staa TP, Egberts AC, et al. Use of alpha-blockers and the risk of hip/femur fractures. J Intern Med 2003;254:548-554.
42. Gotoh M, Kamihira O, Kinukawa T, et al. Comparision of tamsulosin and naftopidil for efficacy and safety in the treatment of benign prostatic hyperplasia: a randomized controlled trial. Br J Urol 2005;96:581-586.
43. Wang JM, McKenna KE, McVary KT, Lee C. Requirement of innervation for maintenance of structural and functional integrity in the rat prostate. Biol Reprod 1991; 44:1171-1176.
44. Rosenzweig-Bublil N, Abramovici A. Stromal fibrosis reaction in rat prostates induced by alpha 1 adrenergic stimulation. J Androl 2006;27:276-284.
45. Bosland MC. Chemical and hormonal induction of prostate cancer in animal models. Urol Oncol 1996;2:103-110.
46. Tuohimaa P. Control of cell proliferation in male accessory sex glands;in E. Spring-Mills and E. S. E. Hafez(eds):Male Accessory Sex Glands. North Holland, Amsterdam. Elsevier,1980, pp 131-153.
47. Ofner P, Bosland MC, Vena RL. Differential effects of diethylstilbestrol and estradiol-17β in combination with testosterone on rat prostate lobes. Toxicol Appl Pharmacol 1992; 112:300-309.
48. Bosland MC, Ford H, Horton L. Induction at high incidence of ductal prostate adenocarcinomas in NBL/Cr and Sprague-Dawley Hsd:SD rats treated with a combination of testosterone and estradiol-17β or diethylstilbestrol. Carcinogenesis 1995;16:1311-1317.
49. Vaalasti A, Alho AM, Tainio H, Hervonen A. The effect of sympathetic denervation with 6-hydroxydopamine on the ventral prostate of the rat. Acta Histochem 1986;79:49-54.
50. James S, Chappie CR, Phillips MI, et al. Autoradiographic analysis of alpha-adrenoceptors and muscarinic cholinergic receptors in the hyperplastic human prostate. J Urol 1989; 142:438-444.
51.Haynes JM, Hill SJ. β-Adrenoceptor-mediated inhibition of α1-adrenoceptor-mediated and field stimulation-induced contractile responses in the prostate of the guinea pig. Br J Pharmacol 1997; 122:1067-1074.
52. Kim JH, Shin SY, Nam JH, et al. Adrenergic regulation of the intracellular [Ca2+] and voltage-operated Ca2+ channel currents in the rat prostate neuroendocrine cells. Prostate 2003;57:99-110.
53.Corvin S, Bosch ST, Eder I, et al. Videoimaging of prostatic stromal-cell contraction: an in vitro model for studying drug effects. Prostate 1998;37:209 -214.
54. Deng XF, Chemtob S, Varma DR. Characterization of a_(1D)-adrenoceptor subtype in rat myocardium, aorta and other tissues. Br J Pharmacol 1996; 119:269-276.
55. Lagu B, Tian D, Jeon Y, et al. De novo design of a novel oxazolidinone analogue as a potent and selective a_(1A) adrenergic receptor antagonist with high oral bioavailability. J Med Chem 2000;43:2775 - 2778.
56. Rees RW, Foxwell NA, Ralph DJ, et al. Y-27632, a Rho kinase inhibitor, inhibits proliferation and adrenergic contraction of prostatic smooth muscle cells. J Urol 2003; 170:2517-2522.
57. Takahashi R, Nishimura J, Seki N, et al. RhoA/Rho kinase-mediated Ca2+ sensitization in the contraction of human prostate. Neurourol urodyn 2007;26:547-51.
58. Mayerhofer A, Bartke A, Steger RW. Catecholamine effects on testicular testosterone production in the gonadally active and the gonadally regressed adult golden hamster. Biol Reprod 1989;40:752-761.
59.Homma Y, Hamada K, Nakayama Y, et al. Effects of castration on contraction and alpha(1)-adrenoceptor expression in rat prostate. Br J Pharmacol 2000;131:1454-1460.
60. Boesch ST, Corvin S, Zhang J, et al. Modulation of the differentiation status of cultured prostatic smooth muscle cells by an alpha1-adrenergic receptor antagonist. Prostate 1999;39:226-233.
61. Farnsworth WE. Prostate stroma: physiology. Prostate 1999;38:60-72.
62.Slater M, Barden JA, Murphy CR. Changes in growth factor expression in the ageing prostate may disrupt epithelial-stromal homeostasis. Histochem J 2000;32: 357-364.
63.Foster CS. Pathology of benign prostatic hyperplasia. Prostate 2000; 45: 4 -14.
64.Yang G, Timme TL, Park SH, et al. Transforming growth factor beta1 transduced mouse prostate reconstitutions: I. Induction of neuronal phenotypes. Prostate 1997;33: 151-156.
65. Guan X-B, McKenna KE, McVary KT. Expression of nerve growth factor in pelvic organs of male rat in response to denervation. Proc Am Urol Assoc 1996;155:536.
66. Keast JR, Kepper ME. Differential regulation of trkA and p75 in noradrenergic pelvic autonomic ganglion cells after deafferentation of their cholinergic neighbours. Eur JNeurosci 2001 ;13:211-220.
67. Liu DT, Reid MT, Bridges DC, et al. Denervation, but not decentralization, reduces nerve growth factor content of the mesenteric artery. J Neurochem 1996;66:2295-2299.
68. Ghafar MA, Shabsigh A, Chichester P, et al. Effects of chronic partial outlet obstruction on blood flow and oxygenation of the rat bladder. J Urol 2002;167:1508-1512.
69. Gatenbeck L. Stress stimuli and the prostatic gland-an experimental study in the rat. Scand J Urol Nephrol Suppl. 1986;99:1-11.
70. Landsberg L. Diet, obesity and hypertension: an hypothesis involving insulin, the sympathetic nervous system, and adaptive thermogenesis. Q J Med 1986;61:1081-1090.
71. Chrousos GP, Gold PW. The concept of stress and stress system disorders. JAMA 1992;267:1244-1252.
72. Karp JD,Smith J, Hawk K: Restraint stress augments antibody production in cyclophosphamide treated mice. Physiol Behav Physico Behav 2000; 70: 271-278.
73. Isobe H, Okajima K, Harada N, et al: Activated protein C reduces stress-induced gastric mucosal injury in rats by inhibiting the endothelial cell injury. J Thromb Haemost 2004;2: 313-320.
74.Boyle P, Napvlkov P. The epidemiology of benign prostatic hyperplasia and observations on concomitant hypertension. Scand J Urol Nephrol Suppl 1995;68:7-12.
75. Hammarsten J, Hogstedt B. Hyperinsulinaemia as a risk factor for developing benign prostatic hyperplsia. Euro Urol 2001;39:151-158.
76. Steers WD, Clemow DB, Persson K, et al. The spontaneously hypertensive rat: insight into the pathogenesis of irritative symptoms in benign prostatic hyperplasia and young anxious males. Experimental Physiology 1999;84:137-147.
77. Clemow DB, Steers WD, McCarty R, et al. Altered regulation of bladder nerve growth factor and neurally mediated hyperactive voiding. Am J Physiol 1998:275:1279-1286.
78. Golomb E, Hill MR, Brown RG, et al. Ouabain enhances the mitogenic effect of serum in vascular smooth muscle cells. Am J Hypertens 1994;7:69-74.
79. Julius S. The evidence for a pathophysiology significance of the sympathetic overactivity in hypertension. Clin Exp Hypertens.1996;18:305-321.
80. Elima R, Malach R, Bergmann F, et al. Hypertension induced by hypothalamic transplantation from genetically hypertensive to normotensive rats. J Neurosci 1991;ll:401-411.
81. Uchino K, Frohlich ED, Nishikimi T, et al. Spontaneously hypertensive rats demonstrate increased renal vascular α1-adrenergic receptor responsiveness. Am J Physiol 1991;260:889-893.
82. Clemow DB, Spitsbergen JM, McCarty R, et al. Altered NGF regulation may link a genetic predisposition for hypertension with hyperactive voiding. J Urol 1999;161:1372-1377.
83. Tarcan T, Azadzoi KM, Siroky MB, et al. Age-related erectile and voiding dysfunction: the role of arterial insufficiency. British Journal of Urology 1998;82(Suppll):26-33.
84. McVary KT. Erectile dysfunction and lower urinary tract symptoms secondary to BPH. European Urology 2005;47:838-845.
85. Yono M, Yamamoto Y, Yoshida M, et al. Effects of doxazosin on blood flow and mRNA expression of nitric oxide synthase in the spontaneously hypertensive rat genitourinary tract. Life Sci 2007;81:218-222.
86. Alvarez MA, Portilla L, Gonzalez IB, Ezcurra E: Insulin response to a short stress period. Psychoneuroendocrinology 1989; 14:241-244.
87. Raikkonen K, Keltikangas J, Hautanen A: The role of psychological coronary risk factors in insulin and glucose metabolism. J Psychosom Res 1994;38:705—713.
88.Reaven GM: Insulin resistance, the insulin resistance syndrome, and cardiovascular disease. Panmiverv Med 2005;47:201-210.
89. Dahle SE, Chokkalingam AP, Gao YT, et al. Body size and serum levels of insulin and leptin in relation to the risk of benign prostatic hyperplasia. J Urol 2002; 168:599-604.
90. Hammarsten J, Hogstedt B. Clinical, anthropometric, metabolic and insulin profile of men with fast annual growth rates of benign prostatic hyperplasia. Blood Pressure 1999;8:29-36.
91. Shieh SM, Sheu WH, Shen DC, et al. Glucose, insulin, and lipid metabolism in doxazosin-treated patients with hypertension. Am J Hypertens 1992;5:827-831.
92. Hautanen A. Synthesis and regulation of sex hormone-binding globulin in obesity. Int J Obes Relat Metab Disord 2000;24:64-70.
93. Peehl DM, Cohen P, Rosenfeld RG. The role of insulin-like growth factors in prostate biology. J Androl 1996; 17:2-4.
94. Toning N, Vinter-Jensen L, Pedersen SB, et al. Systemic administration of insulin-like growth factor I(IGF-I) causes growth of the rat prostate. J Urol1997;158:222-227.
95. Colao A, Marzullo P, Spiezia S, et al. Effect of growth hormone(GH) and insulin-like growth factor I on prostate diseases: an ultrasonographic and endocrine study in acromegaly, GH deficiency, and healthy subjects. J Clin Endocrinol Metab 1999;84:1986-1991.
96. Ketelslegers JM, Maiter D, Maes M, et al. Nutritional regulation of the growth hormone and insulin-like growth factor-binding proteins. Horm Res 1996;45:252-257.
97. Shpakov AO, Plesneva SA, Kuznetsova LA, Pertseva MN. Study of the functional organization of a novel adenylate cyclase signaling mechanism of insulin action. Biochemistry (Mosc) 2002;67:335-342.
98. Pertseva MN, Shpakov AO, Plesneva SA, Kuznetsova LA. A novel view on the mechanisms of action of insulin and other insulin superfamily peptides: involvement of adenylyl cyclase signaling system. Comp Biochem Physiol B Biochem Mol Biol 2003;134:11-36.
99. Ozden C, Ozdal OL, Urgancioglu G, et al. The correlation between metabolic syndrome and prostatic growth in patients with benign proatatic hyperplasia. Eur Urol 2007;51:199-206.
100.Yun AJ, Bazar KA, Lee PY, Gerber A, Daniel SM: The smoking gun: many conditions associated with tobacco exposure may be attributable to paradoxical compensatory autonomic responses to nicotine. Med Hypotheses 2005;64:1073-1079.
101. Untergasser G, Madersbacher S, Berger P. Benign prostatic hyperplasia: age-related tissue-remodeling. Exp Gerontol 2005;40:121-128.
102. Acosta S, Dizeyi N, Pierzynowski S, Aim P, Abrahamsson PA. Neuroendocrine cells and nerves in the prostate of the guinea pig: effects of peripheral denervation and castration. Prostate 2001;46:191-199.
103. Yun AJ, Lee PY, Bazar KA. Can thromboembolism be the result, rather than the inciting cause, of acute vascular events such as stroke, pulmonary embolism, mesenteric ischemia, and venous thrombosis? a maladaptation of the prehistoric trauma response. Med Hypotheses 2005 ;64:706-716.
104. Yun AJ, Lee PY, Bazar KA. Modulation of autonomic balance by tumors and viruses. Med Hypotheses 2004;63:344—351.
105. Nishimura M, Hashimoto T, Kobayashi H, et al. Association between cardiovascular autonomic neuropathy and left ventricular hypertrophy in diabetic hemodialysis patients. Nephrol Dial Transplant 2004;19:2532-2538.
106. Schneyer CA, Humphreys-Beher MG, Jirakulsomchok D, Hall HD. Effects of autonomic antagonists and growth factors on activity-mediated hyperplasia of rat parotid. Am J Physiol 1993;264:G763-766.
1.Purinton PT,Fletcher TF,Bradley WE.Gross and light microscopic features of the pelvic pleus in the rat.Anat Rec 1972;175:697-706.
2.McVary KT,Razzaq A,Lee C,Rademaker A,McKenna KE.Growth of the rat prostate gland is facilitated by the autonomic nervous system.Biol Reprod 1994;51:99-107.
3.Gosling JA.Autonomic innervation of the prostate;in Hinman F(ed):Benign Prostatic Hypertrophy.New York,Springer-Verlag,1983,pp349-360.
4.Wang JM,McKenna KE,Lee C.Determination of prostatic secretion in rats:effect of neurotransmitters and testosterone.The Prostate 1991;18:289-301.
5.Bruschini H,Schmidt RA,Tanagho EA.Neurologic control of prostatic secretion in the dog.Invest Urol 1978;15:288-290.
6.McVary KT,McKenna KE,Lee C.Prostate innervation.Prostate Suppl 1998;8:2-13.
7.Hoffman BB.Adrenoceptor-activating & other sympathomimetic drugs;in Katzung GB(ed):Basic & clinical pharmacology.8th edn.New York,McGraw-Hill Co,2001,pp 120-137.
8.Smith P,Rhodes NP,Beesley C,Ke Y,Foster CS.Prostatic stromal cell phenotype is diercetly modulated by norepinephrine.Urology 1998;51:663-670.
9.Collins MM,Stafford RS,O'Leary MP,Barry MJ.How common is prostatitis? A national survey of physician visits.J Urol 1998;159:1224-1228.
10.Wenninger K,Heiman JR,Rothman I,et al.Sickness impact of chronic nonbacterial prostatitis and its correlates.J Urol 1996;155:965-968.
11.彭轼平:良性前列腺增生概论.见:吴阶平主编;吴阶平泌尿外科学.济南,山东科学技术出版社,2004,1125-1139.
12.Wei JT,Calhoun E,Jacobsen SJ.Urologic Diseases in America project:benign prostatic hyperplasia.J Urol 2005;173:1256-1261.
13.Parkin DM,Bray F,Ferlay J,et al.Global cancer statistics,2002.CA Cancer J Clin 2005;55: 74-108.
14. American Cancer Society. Cancer Facts & Figures 2006. Atlanta: American Cancer Society; 2006.
15. Ferlay J, Bray F, Pisani P, et al. GLOBOCAN 2002 Cancer Incidence, Mortality and Prevalence Worldwide. IARC CancerBase No. 5, version 2. 0. IARCPress, Lyon, 2004.
16.Sidney S, Quesenberry CP Jr, Sadler MC, et al. Incidence of sugically treated benign prostatic hypertrophy and of prostate cancer among blacks and whites in a prepaid health care plan. Am J Epidemiol 1991;134:825-9.
17.Yun AJ, Doux JD. Opening the floodgates: Benign prostatic hyperplasia may represent another disease in the compendium of ailments caused by the global sympathetic bias that emerges with aging. Med Hypotheses 2006;67:392-394.
18.GassR. Benign prostatic hyperplasia: the opposite effects of alcohol and coffee intake. BJU Int 2002;90:649-654.
19.Corti R, Binggeli C, Sudano I, et al. Coffee acutely increases sympathetic nerve activity and blood pressure independently of caffeine content: role of habitual versus nonhabitual drinking. Circulation 2002; 106:2935-2940.
20.Shirao I, Tsuda A, Ida Y, et al. Effect of acute ethanol administration on noradrenaline metabolism in brain regions of stressed and nonstressed rats. Pharmacol Biochem Behav 1988;30:769-773.
21.Hawley RJ, Nemeroff CB, Bissette G, et al. Neurochemical correlates of sympathetic activition during severe alcohol withdrawal. Alcohol Clin Exp Res 1994;18:1312-1316.
22.Verbanck P, Seutin V, Massotte L, et al. Yohimbine can induce ethanol tolerance in an vitro preparation of rat locus coeruleus. Alcohol Clin Exp Res 1991;15:1036-1039.
23.Boyle P, Napvlkov P. The epidemiology of benign prostatic hyperplasia and observations on concomitant hypertension. Scand J Urol Nephrol Suppl 1995;68:7-12.
24.Hammarsten J, Hogstedt B. Hyperinsulinaemia as a risk factor for developing benign prostatic hyperplsia. Euro Urol 2001;39:151-158.
25.Michel MC, Heemann U, Schumacher H, Mehlburger L, Goepel M. Association of hypertension with symptoms of benign prostatic hyperplasia. J Urol 2004;172:1390-1393.
26.Claus S, Berges R, Senge T, et al. Cell kinetic in epithelium and stroma of benign prostatic hyperplasia. J Urol 1997;158:217-221.
27.Kyprianou N. Doxazosin and terazosin suppress prostate growth by inducing apoptosis: clinical significance. J Urol 2003;169:1520-1525.
28.Matityahou A, Rosenzweig N, Golomb E, et al. Rapid proliferation of prostatic epithelial cells in spontaneously hypertensive rats: A model of spontaneous hypertension and prostate hyperplasia. J Androl 2003;24:263-269.
29.Marinese D, Patel R, Walden PD, et al. Mechanistic investigation of the adrenergic induction of ventral prostate hyperplasia in mice. Prostate 2003;54:230-237.
30.Golomb E, Rosenzweig N, Eilam R, et al. Spontaneous hyperplasia of the ventral lobe of the prostate in aging genetically hypertensive rats. J Androl 2000,21:5 8-64.
31 .National Diabetes Information Clearinghouse(NDIC). National Diabetes Statistics. NIH Publication No. 06-3892. November 2005.
32.Krotkiewski M. Role of muscle capillarization and morphology in the development of insulin resistance and metabolic syndrome. Press Med 1994;23:1353-1356.
33.Ozden C, Ozdal OL, Urgancioglu G, et al. The correlation between metabolic syndrome and prostatic growth in patients with benign proatatic hyperplasia. Eur Urol 2007;51:199-206.
34.Dahle SE, Chokkalingam AP, Gao YT, et al. Body size and serum levels of insulin and leptin in relation to the risk of benign prostatic hyperplasia. J Urol 2002;168:599-604.
35. Hammarsten J, Hogstedt B. Clinical, anthropometric, metabolic and insulin profile of men with fast annual growth rates of benign prostatic hyperplasia. Blood Pressure 1999;8:29-36.
36.Landsberg L. Diet, obesity and hypertension: an hypothesis involving insulin, the sympathetic nervous system, and adaptive thermogenesis. Q J Med 1986;61:1081-1090.
37.Shieh SM, Sheu WH, Shen DC, et al. Glucose, insulin, and lipid metabolism in doxazosin-treated patients with hypertension. Am J Hypertens 1992;5:827-831.
38.McVary KT. Erectile dysfunction and lower urinary tract symptoms secondary to BPH. Eur Urol 2005;47:838-845.
39.Hautanen A. Synthesis and regulation of sex hormone-binding globulin in obesity. Int J Obes Relat Metab Disord 2000;24:64-70.
40.Peehl DM, Cohen P, Rosenfeld RG The role of insulin-like growth factors in prostate biology. J Androl 1996; 17:2-4.
41.Toning N, Vinter-Jensen L, Pedersen SB, et al. Systemic administration of insulin-like growth factor I(IGF-I) causes growth of the rat prostate. J Urol 1997; 158:222-227.
42.Colao A, Marzullo P, Spiezia S, et al. Effect of growth hormone(GH) and insulin-like growth factor I on prostate diseases: an ultrasonographic and endocrine study in acromegaly, GH deficiency, and healthy subjects. J Clin Endocrinol Metab 1999;84:1986-1991.
43. Shpakov AO, Plesneva SA, Kuznetsova LA, Pertseva MN. Study of the functional organization of a novel adenylate cyclase signaling mechanism of insulin action. Biochemistry (Mosc) 2002;67:335-342.
44. Pertseva MN, Shpakov AO, Plesneva SA, Kuznetsova LA. A novel view on the mechanisms of action of insulin and other insulin superfamily peptides: involvement of adenylyl cyclase signaling system. Comp Biochem Physiol B Biochem Mol Biol 2003; 134:11-36.
45.Nandeesha H, Koner BC, Dorairajan LN, et al. Hyperinsulinemia and dyslipidemia in non-diabetic benign prostatic hyperplasia. Clin Chim Acta 2006;370:89-93.
46.Rosen RC, Giuliano F, Carson CC. Sexual dysfunction and lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH). Eur Urol 2005;47:824-837.
47.Feldman HA, Goldstein I, Hatzichristou DG, et al. Impotence and its medical and psychosocial correlates: results of the Massachusetts Male Aging Study. J Urol 1994;151:54-61.
48.Nicolosi A, Glasser DB, Moreira ED, et al. Prevalence of erectile dysfunction and associated factors among men without concomitant diseases: a population study. Int J Impot Res 2003;15:253-257.
49.Rosen R, Altwein J, Boyle P, et al. Lower urinary tract symptoms and male sexual dysfunction: the multinational survey of the aging male(MSAM-7). Eur Urol 2003;44:637-649.
50. Hieble JP, Bylund DB, Clarke DE, et al. International Union of Pharmacology X. Recommendation for nomenclature of a1-adrenoceptors: Consensus update. Pharmacol Rev 1995;47:267-270.
51 .Hawrylyshyn KA, Michelotti GA, Coge F, et al. Update on human alpha1-adrenoceptor subtype signaling and genomic organization. Trends Pharmacol Sci 2004;25:449-455.
52. Price DT, Lefkowitz RJ, Caron MG, et al. Localization of mRNA for three distinct alpha 1-adrenergic receptor subtypes in human tissues: implications for human alpha-adrenergic physiology. Mol Pharmacol 1994; 45: 171-175.
53. Kojima Y, Sasaki S, Shinoura H, et al. Change of expression levels of alpha 1-adrenoceptor subtypes by administration of alphald-adrenoceptor-subtype-selective antagonist naftopidil in benign prostate hyperplasia patients. Prostate 2007;67:1285-1292.
54. Smith M, Schambra U, Wilson K, et al. Alpha 1-adrenergic receptors in human spinal cored: specific localized expression of mRNA encoding alpha 1-adrenergic receptor subtypes at four distinct levels. Mol Brain Res 1999;63:254-261.
55.Bouchelouche K, Andersen L, Alvarez S, et al. Increased contractile response to phenylephrine in detrusor of patients with bladder outlet obstruction: effect of the alphal A and alphal D-adrenergic receptor antagonist tamsulosin. J Urol 2005;173:657-661.
56.Souverein PC, Van Staa TP, Egberts AC, et al. Use of alpha-blcckers and the risk of hip/femur fractures. J Intern Med 2003;254:548-554.
57.Gotoh M, Kamihira O, Kinukawa T, et al. Comparision of tamsulosin and naftopidil for efficacy and safety in the treatment of benign prostatic hyperplasia: a randomized controlled trial. Br J Urol 2005;96:581-586.
58. Vaalasti A, Alho AM, Tainio H, et al. The effect of sympathetic denervation with 6-hydroxydopamine on the ventral prostate of the rat. Acta Histochem 1986;79:49-54.
59.Mayerhofer A, Bartke A, Steger RW. Catecholamine effects on testicular testosterone production in the gonadally active and the gonadally regressed adult golden hamster. Biol Reprod 1989;40:752-761.
60.Homma Y, Hamada K, Nakayama Y, et al. Effects of castration on contraction and alpha(1)-adrenoceptor expression in rat prostate. Br J Pharmacol 2000;131:1454-1460.
61.Farnsworth WE. Prostate stroma: physiology. Prostate 1999;38:60-72.
62.Slater M, Barden JA, Murphy CR. Changes in growth factor expression in the ageing prostate may disrupt epithelial-stromal homeostasis. Histochem J 2000;32: 357-364.
63.Foster CS. Pathology of benign prostatic hyperplasia. Prostate 2000; 45: 4 -14.
64.Yang G, Timme TL, Park SH, et al. Transforming growth factor betal transduced mouse prostate reconstitutions: I. Induction of neuronal phenotypes. Prostate 1997;33: 151-156.
65.Ghafar MA, Shabsigh A, Chichester P, et al. Effects of chronic partial outlet obstruction on blood flow and oxygenation of the rat bladder. J Urol 2002;167:1508-1512.
66.Clemow DB, Steers WD, McCarty R, et al. Altered regulation of bladder nerve growth factor and neurally mediated hyperactive voiding. Am J Physiol 1998;275:1279-1286.
67.Golomb E, Hill MR, Brown RG, et al. Ouabain enhances the mitogenic effect of serum in vascular smooth muscle cells. Am J Hypertens 1994;7:69-74.
68.Julius S. The evidence for a pathophysiology significance of the sympathetic overactivity in hypertension. Clin Exp Hypertens.1996;18:305-321.
69.Elima R, Malach R, Bergmann F, et al. Hypertension induced by hypothalamic transplantation from genetically hypertensive to normotensive rats. J Neurosci 1991;11:401-411.
70.Uchino K, Frohlich ED, Nishikimi T, et al. Spontaneously hypertensive rats demonstrate increased renal vascular α1-adrenergic receptor responsiveness. Am J Physiol 1991;260:889-893.
71.Golomb E, Kruglikova A, Dvir D, et al. Induction of atypical prostatic hyperplasia in rats by sympathomimetic stimulation. Prostate 1998;34:214-221.
72.Kyprianou N, Litvak JP, Borkowski A, et al. Induction of prostate apoptosis by doxazosin in benign prostatic hyperplasia. J Urol 1998; 159:1810-1815.
73.Clemow DB, Spitsbergen JM, McCarty R, et al. Altered NGF regulation may link a genetic predisposition for hypertension with hyperactive voiding. J Urol 1999;161:1372-1377.
74.McVary KT, Rademaker A, Lloyd GL, et al. Autonomic nervous system overactivity in men with lower urinary tract symptoms secondary to benign prostatic hyperplasia. J Urol 2005;174:1327-1333.
75.Ullich PM, Lutgendorf SK, Kreder KJ. Physiologic reactivity to a laboratory stress task among men with benign prostatic hyperplasia. Urology 2007;70:487-492.
76.Bjorntorp P. Body fat distribution, insulin resistance, and metabolic disease. Nutrition 1997; 13:795-803.
1.Lee CL, Kozlowski JM, Grayhack JT: Etiology of benign prostate hyperplasia. Urol Clin North Am 1995;22:237-246.
2.Lepor H: Alpha blockage for the treatment of benign prostatic hyperplasia. Urol Clin North Am 1995;22:375-386.
3.Chrousos GP, Gold PW: The concept of stress and stress system disorders. JAMA 1992;267:1244-1252.
4.Krieger JN: Classification, epidemiology and implications of chronic prostatitis in North America, Europe and Asia. Minerva Urol Nefrol 2004;56:99-104.
5.Badalyan RR, Fanarjyan SV, Aghajanyan IG: Chlamydial and ureaplasmal infections in patients with nonbacterial chronic prostatitis. Andrologia 2003;35:263-265.
6.Rudnick DH: Stress cause of prostatitis. Urology. 1985;26:320-1.
7.Gatenbeck L: Stress stimuli and the prostatic gland-an experimental study in the rat. Scand J Urol Nephrol Suppl. 1986;99:1-11.
8.McVary KT, Rademaker A, Lloyd GL, Gaan P: Autonomic nervous system overactivity in men with lower urinary tract symptoms secondary to benign prostatic hyperplasia. J Urol 2005;174:1327-1333.
9.Ullrich PM, Lutgendorf SK, Kreder KJ: Physiologic reactivity to a laboratory stress task among men with benign prostatic hyperplasia. Urology 2007;70:487-491.
10.Walsh PC, Retic AB, Stamey TA, Vaughan ED: Benign prostate hyperplasia;in Walsh PC, Retic AB, Stamey TA, Vaughan ED(eds): Campbell's Urology, 6th ed. Philadelphia, WB. Saunders,1992, pp 1014-1015.
11.Ozden C, Ozdal OL, Urgancioglu G, Koyuncu H, Gokkaya S, Memis A: The correlation between metabolic syndrome and prostatic growth in patients with benign prostatic hyperplasia. Eur Urol 2007;51:199-206.
12.Reaven GM: Insulin resistance, the insulin resistance syndrome, and cardiovascular disease. Panmiverv Med 2005;47:201-210.
13. Alvarez MA, Portilla L, Gonzalez IB, Ezcurra E: Insulin response to a short stress period. Psychoneuroendocrinology 1989;14:241—244.
14. Raikkonen K, Keltikangas J, Hautanen A: The role of psychological coronary risk factors in insulin and glucose metabolism. J Psychosom Res 1994;38:705—713.
15.McVary KT, McKenna KE, Lee C: Prostate innervation. Prostate 1998;8 (suppl):2-13.
16.Vaalasti A, Alho AM, Tainio H, Hervonen A: The effect of sympathetic denervation with 6-hydroxydopamine on the ventral prostate of the rat. Acta Histochem 1986;79:49-54.
17.Shibata Y, Kashiwagi B, Ono Y, Fukabori Y, Suzuki K, Honma S, Yamanaka H: The evaluation of rat prostate blood flow using a laser speckle flowmetry: a comparative study using the microsphere method in castrated and androgen-replenished rats. Urol Res 2004;32:44-8.
18.Wilson MJ, Woodson M, Wiehr C, Reddy A, Sinha AA: Matrix metalloproteinases in the pathogenesis of estradiol-induced nonbacterial prostatitis in the lateral prostate lobe of the Wistar rat. Exp Mol Pathol 2004;77:7-17.
19.Purinton PT, Fletcher TF, Bradley WE: Gross and light microscopic features of the pelvic pleus in the rat. Anat Rec 1972;175:697-706.
20.McVary KT, Razzaq A, Lee C, Rademaker A, McKenna KE: Growth of the rat prostate gland is facilitated by the autonomic nervous system. Biol Reprod 1994;51:99-107.
21.Gosling JA: Autonomic innervation of the prostate;in Hinman F(ed):Benign Prostatic Hypertrophy. New York, Springer-Verlag,1983,pp349-360.
22.Wang JM, McKenna KE, Lee C: Determination of prostatic secretion in rats: effect of neurotransmitters and testerone. Prostate 1991;18:289-301.
23.Jin Y, Chuan W, Ali Y: The plasma corticosterone in rats during physical and psychological stress. Acta Psychological Sinica 1991 ;4 :418-425.
24.Karp JD,Smith J, Hawk K: Restraint stress augments antibody production in cyclophosphamide treated mice. Physiol Behav Physico Behav 2000; 70: 271-278.
25. Schommer NC , Hellhammer DH, Kirschbaum C: Dissociation between reactivity of the hypothalamus - pituitary - adrenal axis and the sympathetic-adrenal-medullary system to repeated psychosocial stress. Psychosom Med 2003 ;65 :450 - 460.
26.Pei ZH, Zhu MZ, Pei JM, Gao Z, Lv SY: To detect the contents of mice plasma catecholamine by the high efficient liquid chromatography. Chin Heart 2003; 15:9-11.
27. Rosenzweig N, Horodniceanu J, Abramovici A: Phenylephrine-induced neurogenic prostatitis facilitates the promotion of PIN-like lesions in rats.Prostate 2004;59:107-113.
28.Golomb E, Rosenzweig N, Eilam R, Abramovici A: Spontaneous hyperplasia of the ventral lobe of the prostate in aging genetically hypertensive rats. J Androl 2000;21:58-64.
29.Boyle P, Napalkov P: The epidemiology of benign prostatic hyperplasia and observation on concomitant hypertension. Scand J Urol Nephrol 1995;168:7-12.
30.Gass R: Benign prostatic hyperplasia: the opposite effects of alcohol and coffee intake. BJU Int 2002;90:649-654.
31.Yun AJ, Bazar KA, Lee PY, Gerber A, Daniel SM: The smoking gun: many conditions associated with tobacco exposure may be attributable to paradoxical compensatory autonomic responses to nicotine. Med Hypotheses 2005;64:1073-1079.
32.Meigs JB, Mohr B, Barry MJ, Collins MM, McKinlay JB: Risk factors for clinical benign prostatic hyperplasia in a community-based population of healthy aging men. J Clin Epidemiol 2001;54:935-944.
1. Snider WD (1994) Functions of the neurotrophins during nervous system development: what the knockouts are teaching us. Cell 77:627-638
2.Paul AB, Grant ES, Habib FK (1996) The expression and localization of β-nerve growth factor (β-NGF) in benign and malignant human prostate tissue: relationship to neuroendocrine differentiation. Br J Cancer 74:1990-1996
3.Guan X-B, McKenna KE, McVary KT (1996) Expression of nerve growth factor in pelvic organs of male rat in response to denervation. Proc Am Urol Assoc Suppl 155:536
4.Li C, Watanabe G, Weng Q et al (2005) Expression of nerve growth factor (NGF), and its receptors trkA and p75 in the reproductive organs of the adult male rats. Zoolog Sci 22:933-937
5.Vaalasti A, Alho AM, Tainio H et al (1986) The effect of sympathetic denervation with 6-hydroxydopamine on the ventral prostate of the rat. Acta Histochem 79:49-54
6.Karp JD, Smith J, Hawk K (2000) Restraint stress augments antibody production in cyclophosphamide treated mice. Physiol Behav 70:271-8
7.Murphy RA, Watson AY, Rhodes JA (1984) Biological sources of nerve growth factor. Appl Neurophysiol 47:33-42
8.Djakiew D, Delsite R, Pflug B et al (1991) Regulation of growth by a nerve growth factor-like protein which modulates paracrine interactions between a neoplastic epithelial cell line and stromal cells of the human prostate. Cancer Res 51:3304-3310
9.Graham CW, Lynch JH, Djakiew D (1992) Distribution of nerve growth factor-like protein and nerve growth factor receptor in human prostatic hyperplasia and prostatic carcinoma. J Urol 147:1444-1447
10.Liu DT, Reid MT, Bridges DC et al (1996) Denervation, but not decentralization, reduces nerve growth factor content of the mesenteric artery. J Neurochem 66:2295-2299
11.Golomb E, Rosenzweig N, Eilam R et al (2000) Spontaneous hyperplasia of the ventral lobe of the prostate in aging genetically hypertensive rats. J Androl 21:58-64
12.Clemow DB, Steers WD, McCarty R et al (1998) Altered regulation of bladder nerve growth factor and neurally mediated hyperactive voiding. Am J Physiol 275:1279-1286
13.Kim JC, Park EY, Hong SH et al (2005) Changes of urinary nerve growth factor and prostaglandins in male patients with overactive bladder symptom. Int J Urol 12:875-880
14.Kim JC, Park EY, Seo SI et al (2006) Nerve growth factor and prostaglandins in the urine of female patients with overactive bladder. J Urol 175:1773-1776
15.Djakiew D (2000) Dysregulated expression of growth factors and their receptors in the development of prostate cancer. Prostate 42:150-160
16.Dalal R, Djakiew D (1997) Molecular characterization of neurotrophin expression and the corresponding tropomyosin receptor kinases (trks) in epithelial and stromal cells of the human prostate. Mol Cell Endocrinol 134:15-22
1.McVary KT, McKenna KE, Lee C: Prostate innervation. Prostate 1998;8 (suppl):2-13.
2.McVary KT, Razzaq A, Lee C, Rademaker A, McKenna KE: Growth of the rat prostate gland is facilitated by the autonomic nervous system. Biol Reprod 1994;51:99-107.
3.Beduschi MC, Beduschi R, Oesterling JE: Alpha-blockade therapy for benign prostatic hyperplasia: from a nonselective to a more selective alpha 1A-adrenergic antagonist. Urology 1998;51:861-872.
4.Owman C, Sjostrand NO: Short adrenergic neurons and catecholamine-containing cells in vas deferens and accessory male genital glands of different mammals. Z Zellforsch 1965;66:300-320.
5.Vaalasti A, Hervonen A: Autonomic innervation of the human prostate. Invest Urol 1980;17:293-297.
6.Vaalasti A, Hervonen A: Nerve endings in the human prostate. Am J Anat 1980;157:41-47.
7.Gosling JA: Autonomic innervation of the prostate;in Hinman F(ed):Benign Prostatic Hypertrophy. New York, Springer-Verlag,1983,pp349-360.
8.Lepor H, Shapiro E, Bowsher RR, Henry DP: Determination of norepinephrine levels in the adult human prostate. J Urol 1990; 144:1263-1266.
9.Tong YC, Hung YC, Lin SN, Cheng JT: The norepinephrine tissue concentration and neuropeptide Y immunoreactivity in genitourinary organs of the spontaneously hypertensive rat. J Auton Nerv Syst 1996;56:215-218.
10.Hieble JP, Bylund DB, Clarke DE, Eikenburg DC, Langer SZ, Lefkowitz RJ, Minneman KP, Ruffolo RR: International union of pharmacology X. Recommendation for nomenclature of alpha1-adrenoceptors: consensus update. Pharmacol. Rev. 1995; 47: 267-70.
11.Walden PD, Durkin MM, Lepor H, Wetzel JM, Gluchowski C, Gustafson EL: Localization of mRNA and receptor binding sites for the a1a-adrenoceptor subtype in the rat, monkey, and human urinary bladder and prostate. J Urol 1997;157:1032-1038.
12.Price DT, Schwinn DA, Lomasney JW, Allen LF, Caron MG, Lefkowitz RJ. Identification, quantification, and localization of mRNA for three distinct al adrenergic receptor subtypes in human prostate. J Urol 1993; 150:546-551.
13.Jacobs SC, Story MT: Exocrine secretion of epidermal growth factor by the rat prostate: Effect of adrenergic agents, cholinergic agents and vasoactive intestinal peptide. Prostate 1988; 13:79-87.
14.Smith P, Rhodes NP, Beesley C, Ke Y, Foster CS: Prostatic stromal cell phenotype is diercetly modulated by norepinephrine. Urology 1998;51:663-670.
15.Litvak JP, Borkowski A, Jacobs SC, Kyprianou N: Induction of prostate apoptosis by doxazosin: Targeting alpha 1 blockade in benign prostatic hyperplasia. J Urol 1997;157:279.
16.Golomb E, Rosenzweig N, Eilam R, Abramovici A: Spontaneous hyperplasia of the ventral lobe of the prostate in aging genetically hypertensive rats. J Androl 2000;21:58-64.
17.Clemow DB, Spitsbergen JM, McCarty R, Steers WD, Turtle JB: Altered NGF regulation may link a genetic predisposition for hypertension with hyperactive voiding. J Urol 1999; 161:1372-1377.
18.McVary KT, Rademaker A, Lloyd GL, Gaan P: Autonomic nervous system overactivity in men with lower urinary tract symptoms secondary to benign prostatic hyperplasia. J Urol 2005;174:1327-1333.
19.Ullrich PM, Lutgendorf SK, Kreder KJ: Physiologic reactivity to a laboratory stress task among men with benign prostatic hyperplasia. Urology 2007;70:487-491.
20.Marinese D, Patel R, Walden PD. Mechanistic investigation of the adrenergic induction of ventral prostate hyperplasia in mice. Prostate 2003;54:230-237.
21.Ghafar MA, Shabsigh A, Chichester P, Anastasiadis AG, Borow A, Levin RM, Buttyan R. Effects of chronic partial outlet obstruction on blood flow and oxygenation of the rat bladder. J Urol 2002;167:1508-1512.
22.Alvarez MA, Portilla L, Gonzalez IB, Ezcurra E: Insulin response to a short stress period. Psychoneuroendocrinology 1989;14:241—244.
23.Raikkonen K, Keltikangas J, Hautanen A: The role of psychological coronary risk factors in insulin and glucose metabolism. J Psychosom Res 1994;38:705-713.
24.Reaven GM: Insulin resistance, the insulin resistance syndrome, and cardiovascular disease. Panmiverv Med 2005;47:201-210.
25.Gass R: Benign prostatic hyperplasia: the opposite effects of alcohol and coffee intake. BJU Int 2002;90:649-654.
26.Yun AJ, Bazar KA, Lee PY, Gerber A, Daniel SM: The smoking gun: many conditions associated with tobacco exposure may be attributable to paradoxical compensatory autonomic responses to nicotine. Med Hypotheses 2005;64:1073-1079.
27.Meigs JB, Mohr B, Barry MJ, Collins MM, McKinlay JB: Risk factors for clinical benign prostatic hyperplasia in a community-based population of healthy aging men. J Clin Epidemiol 2001;54:935-944.
2. McVary KT, McKenna KE, Lee C. Prostate innervation. Prostate Suppl 1998;8:2-13.
3. Vaalasti A, Hervonen A. Autonomic innervation of the human prostate. Invest Urol 1980;17:293-297.
4. Purinton PT, Fletcher TF, Bradley WE. Gross and light microscopic features of the pelvic pleus in the rat. Anat Rec 1972;175:697-706.
5. Lepor H, Shapiro E, Bowsher RR, Henry DP: Determination of norepinephrine levels in the adult human prostate. J Urol 1990;144:1263-1266.
6. Tong YC, Hung YC, Lin SN, Cheng JT: The norepinephrine tissue concentration and neuropeptide Y immunoreactivity in genitourinary organs of the spontaneously hypertensive rat. J AutonNerv Syst 1996;56:215—218.
7. Hieble JP, Bylund DB, Clarke DE, Eikenburg DC, Langer SZ, Lefkowitz RJ, Minneman KP, Ruffolo RR: International union of pharmacology X. Recommendation for nomenclature of alpha1-adrenoceptors: consensus update. Pharmacol. Rev. 1995; 47: 267-70.
8. Marinese D, Patel R, Walden PD, et al. Mechanistic investigation of the adrenergic induction of ventral prostate hyperplasia in mice. Prostate 2003;54:230-237.
9. McVary KT, Razzaq A, Lee C, Rademaker A, McKenna KE. Growth of the rat prostate gland is facilitated by the autonomic nervous system. Biol Reprod 1994;51:99-107.
10. Jacobs SC, Story MT: Exocrine secretion of epidermal growth factor by the rat prostate: Effect of adrenergic agents, cholinergic agents and vasoactive intestinal peptide. Prostate 1988; 13:79-87.
11. Smith P, Rhodes NP, Beesley C, Ke Y, Foster CS. Prostatic stromal cell phenotype is diercetly modulated by norepinephrine. Urology 1998;51:663-670.
12. Kyprianou N, Litvak JP, Borkowski A, et al. Induction of prostate apoptosis by doxazosin in benign prostatic hyperplasia. J Urol 1998;159:1810-1815.
13. Kyprianou N. Doxazosin and terazosin suppress prostate growth by inducing apoptosis: clinical significance. J Urol 2003;169:1520-1525.
14. Golomb E, Kruglikova A, Dvir D, et al. Induction of atypical prostatic hyperplasia in rats by sympathomimetic stimulation. Prostate 1998;34:214-221.
15. GassR. Benign prostatic hyperplasia: the opposite effects of alcohol and coffee intake. BJU Int 2002;90:649-654.
16. Mc Vary KT, Rademaker A, Lloyd GL, et al. Autonomic nervous system overactivity in men with lower urinary tract symptoms secondary to benign prostatic hyperplasia. J Urol 2005;174:1327-1333.
17. Ullrich PM, Lutgendorf SK, Kreder KJ: Physiologic reactivity to a laboratory stress task among men with benign prostatic hyperplasia. Urology 2007;70:487-491.
18. Meigs JB, Mohr B, Barry MJ, Collins MM, McKinlay JB: Risk factors for clinical benign prostatic hyperplasia in a community-based population of healthy aging men. J Clin Epidemiol 2001;54:935-944.
19. Golomb E, Rosenzweig N, Eilam R, et al. Spontaneous hyperplasia of the ventral lobe of the prostate in aging genetically hypertensive rats. J Androl 2000,21:58-64.
20. Clemow DB, Spitsbergen JM, McCarty R, et al. Altered NGF regulation may link a genetic predisposition for hypertension with hyperactive voiding. J Urol 1999;161:1372-1377.
21. Snider WD. Functions of the neurotrophins during nervous system development: what the knockouts are teaching us. Cell 1994;77:627-638
22. Paul AB, Grant ES, Habib FK. The expression and localization of P-nerve growth factor (P-NGF) in benign and malignant human prostate tissue: relationship to neuroendocrine differentiation. Br J Cancer 1996;74:1990-1996
23. Dalai R, Djakiew D. Molecular characterization of neurotrophin expression and the corresponding tropomyosin receptor kinases (trks) in epithelial and stromal cells of the human prostate. Mole Cell Endocrinol 1997;134:15-22.
24. Li C, Watanabe G, Weng Q, et al. Expression of nerve growth factor (NGF), and its receptors TrkA and p75 in the reproductive organs of the adult male rats. Zoolog Sci 2005;22:933-937.
25. Eyres HM. Nervous retention of urine. BMJ 1912;1:484-487.
26. Gosling JA. Autonomic innervation of the prostate;in Hinman F(ed):Benign Prostatic Hypertrophy. New York, Springer-Verlag,1983,pp349-360.
27. Wang JM, McKenna KE, Lee C. Determination of prostatic secretion in rats: effect of neurotransmitters and testosterone. The Prostate 1991; 18:289-301.
28. Bruschini H, Schmidt RA, Tanagho EA. Neurologic control of prostatic secretion in the dog. Invest Urol 1978; 15:288-290.
29. Keast JR, Luckensmeyer GB, Schemann M. All pelvic neurons in male rats contain synthetic enzymes for either noradrenaline or acetylcholine. Neurosci Lett 1995; 196:209-212.
30. Hedlund P. Nitric oxide/cGMP-mediated eVects in the out-flow region of the lower urinary tract - is there a basis for pharmacological targeting of cGMP? World J Urol 2005;23:362-367.
31. Andersson KE. LUTS treatment: future treatment options. Neurourol Urodyn 2007;26:928-933.
32. Michel MC, Vrydag W. Alphal-, alpha2- and beta-adrenoceptors in the urinary bladder, urethra and prostate. Br J Pharmacol 2006;147:88-119.
33. Hawrylyshyn KA, Michelotti GA, Coge F, et al. Update on human alpha1-adrenoceptor subtype signaling and genomic organization. Trends Pharmacol Sci 2004;25:449-455.
34. Price DT, Lefkowitz RJ, Caron MG, et al. Localization of mRNA for three distinct alpha 1-adrenergic receptor subtypes in human tissues: implications for human alpha-adrenergic physiology. Mol Pharmacol 1994; 45: 171-175.
35. Lepor H, Zhang W, Kobayashi S, et al. A comparison of the binding and functional properties of alpha-1 adrenoceptors and area density of smooth muscle in the human, canine and rat prostate. J Pharmacol Exp Ther 1994; 270:722-727.
36. Shapiro E, Becich MJ, Hartanto V. The relative proportion of stromal and epithelial hyperplasia is related to the development of symptomatic benign prostatic hyperplasia. J Urol 1992;147:1293-1297.
37. Roehrborn CG, Schwinn DA. al-Adrenergic receptors and their inhibitors in lower urinary tract symptoms and benign prostatic hyperplasia. J Urol 2004;171:1029-1035.
38.Kojima Y, Sasaki S, Shinoura H, et al. Change of expression levels of alpha1-adrenoceptor subtypes by administration of alpha1d-adrenoceptor-subtype-selective antagonist naftopidil in benign prostate hyperplasia patients. Prostate 2007;67:1285-1292.
39. Smith M, Schambra U, Wilson K, et al. Alphal-adrenergic receptors in human spinal cored: specific localized expression of mRNA encoding alphal-adrenergic receptor subtypes at four distinct levels. Mol Brain Res 1999;63:254-261.
40. Bouchelouche K, Andersen L, Alvarez S, et al. Increased contractile response to phenylephrine in detrusor of patients with bladder outlet obstruction: effect of the alphal A and alphal D-adrenergic receptor antagonist tamsulosin. J Urol 2005;173:657-661.
41. Souverein PC, Van Staa TP, Egberts AC, et al. Use of alpha-blockers and the risk of hip/femur fractures. J Intern Med 2003;254:548-554.
42. Gotoh M, Kamihira O, Kinukawa T, et al. Comparision of tamsulosin and naftopidil for efficacy and safety in the treatment of benign prostatic hyperplasia: a randomized controlled trial. Br J Urol 2005;96:581-586.
43. Wang JM, McKenna KE, McVary KT, Lee C. Requirement of innervation for maintenance of structural and functional integrity in the rat prostate. Biol Reprod 1991; 44:1171-1176.
44. Rosenzweig-Bublil N, Abramovici A. Stromal fibrosis reaction in rat prostates induced by alpha 1 adrenergic stimulation. J Androl 2006;27:276-284.
45. Bosland MC. Chemical and hormonal induction of prostate cancer in animal models. Urol Oncol 1996;2:103-110.
46. Tuohimaa P. Control of cell proliferation in male accessory sex glands;in E. Spring-Mills and E. S. E. Hafez(eds):Male Accessory Sex Glands. North Holland, Amsterdam. Elsevier,1980, pp 131-153.
47. Ofner P, Bosland MC, Vena RL. Differential effects of diethylstilbestrol and estradiol-17β in combination with testosterone on rat prostate lobes. Toxicol Appl Pharmacol 1992; 112:300-309.
48. Bosland MC, Ford H, Horton L. Induction at high incidence of ductal prostate adenocarcinomas in NBL/Cr and Sprague-Dawley Hsd:SD rats treated with a combination of testosterone and estradiol-17β or diethylstilbestrol. Carcinogenesis 1995;16:1311-1317.
49. Vaalasti A, Alho AM, Tainio H, Hervonen A. The effect of sympathetic denervation with 6-hydroxydopamine on the ventral prostate of the rat. Acta Histochem 1986;79:49-54.
50. James S, Chappie CR, Phillips MI, et al. Autoradiographic analysis of alpha-adrenoceptors and muscarinic cholinergic receptors in the hyperplastic human prostate. J Urol 1989; 142:438-444.
51.Haynes JM, Hill SJ. β-Adrenoceptor-mediated inhibition of α1-adrenoceptor-mediated and field stimulation-induced contractile responses in the prostate of the guinea pig. Br J Pharmacol 1997; 122:1067-1074.
52. Kim JH, Shin SY, Nam JH, et al. Adrenergic regulation of the intracellular [Ca2+] and voltage-operated Ca2+ channel currents in the rat prostate neuroendocrine cells. Prostate 2003;57:99-110.
53.Corvin S, Bosch ST, Eder I, et al. Videoimaging of prostatic stromal-cell contraction: an in vitro model for studying drug effects. Prostate 1998;37:209 -214.
54. Deng XF, Chemtob S, Varma DR. Characterization of a_(1D)-adrenoceptor subtype in rat myocardium, aorta and other tissues. Br J Pharmacol 1996; 119:269-276.
55. Lagu B, Tian D, Jeon Y, et al. De novo design of a novel oxazolidinone analogue as a potent and selective a_(1A) adrenergic receptor antagonist with high oral bioavailability. J Med Chem 2000;43:2775 - 2778.
56. Rees RW, Foxwell NA, Ralph DJ, et al. Y-27632, a Rho kinase inhibitor, inhibits proliferation and adrenergic contraction of prostatic smooth muscle cells. J Urol 2003; 170:2517-2522.
57. Takahashi R, Nishimura J, Seki N, et al. RhoA/Rho kinase-mediated Ca2+ sensitization in the contraction of human prostate. Neurourol urodyn 2007;26:547-51.
58. Mayerhofer A, Bartke A, Steger RW. Catecholamine effects on testicular testosterone production in the gonadally active and the gonadally regressed adult golden hamster. Biol Reprod 1989;40:752-761.
59.Homma Y, Hamada K, Nakayama Y, et al. Effects of castration on contraction and alpha(1)-adrenoceptor expression in rat prostate. Br J Pharmacol 2000;131:1454-1460.
60. Boesch ST, Corvin S, Zhang J, et al. Modulation of the differentiation status of cultured prostatic smooth muscle cells by an alpha1-adrenergic receptor antagonist. Prostate 1999;39:226-233.
61. Farnsworth WE. Prostate stroma: physiology. Prostate 1999;38:60-72.
62.Slater M, Barden JA, Murphy CR. Changes in growth factor expression in the ageing prostate may disrupt epithelial-stromal homeostasis. Histochem J 2000;32: 357-364.
63.Foster CS. Pathology of benign prostatic hyperplasia. Prostate 2000; 45: 4 -14.
64.Yang G, Timme TL, Park SH, et al. Transforming growth factor beta1 transduced mouse prostate reconstitutions: I. Induction of neuronal phenotypes. Prostate 1997;33: 151-156.
65. Guan X-B, McKenna KE, McVary KT. Expression of nerve growth factor in pelvic organs of male rat in response to denervation. Proc Am Urol Assoc 1996;155:536.
66. Keast JR, Kepper ME. Differential regulation of trkA and p75 in noradrenergic pelvic autonomic ganglion cells after deafferentation of their cholinergic neighbours. Eur JNeurosci 2001 ;13:211-220.
67. Liu DT, Reid MT, Bridges DC, et al. Denervation, but not decentralization, reduces nerve growth factor content of the mesenteric artery. J Neurochem 1996;66:2295-2299.
68. Ghafar MA, Shabsigh A, Chichester P, et al. Effects of chronic partial outlet obstruction on blood flow and oxygenation of the rat bladder. J Urol 2002;167:1508-1512.
69. Gatenbeck L. Stress stimuli and the prostatic gland-an experimental study in the rat. Scand J Urol Nephrol Suppl. 1986;99:1-11.
70. Landsberg L. Diet, obesity and hypertension: an hypothesis involving insulin, the sympathetic nervous system, and adaptive thermogenesis. Q J Med 1986;61:1081-1090.
71. Chrousos GP, Gold PW. The concept of stress and stress system disorders. JAMA 1992;267:1244-1252.
72. Karp JD,Smith J, Hawk K: Restraint stress augments antibody production in cyclophosphamide treated mice. Physiol Behav Physico Behav 2000; 70: 271-278.
73. Isobe H, Okajima K, Harada N, et al: Activated protein C reduces stress-induced gastric mucosal injury in rats by inhibiting the endothelial cell injury. J Thromb Haemost 2004;2: 313-320.
74.Boyle P, Napvlkov P. The epidemiology of benign prostatic hyperplasia and observations on concomitant hypertension. Scand J Urol Nephrol Suppl 1995;68:7-12.
75. Hammarsten J, Hogstedt B. Hyperinsulinaemia as a risk factor for developing benign prostatic hyperplsia. Euro Urol 2001;39:151-158.
76. Steers WD, Clemow DB, Persson K, et al. The spontaneously hypertensive rat: insight into the pathogenesis of irritative symptoms in benign prostatic hyperplasia and young anxious males. Experimental Physiology 1999;84:137-147.
77. Clemow DB, Steers WD, McCarty R, et al. Altered regulation of bladder nerve growth factor and neurally mediated hyperactive voiding. Am J Physiol 1998:275:1279-1286.
78. Golomb E, Hill MR, Brown RG, et al. Ouabain enhances the mitogenic effect of serum in vascular smooth muscle cells. Am J Hypertens 1994;7:69-74.
79. Julius S. The evidence for a pathophysiology significance of the sympathetic overactivity in hypertension. Clin Exp Hypertens.1996;18:305-321.
80. Elima R, Malach R, Bergmann F, et al. Hypertension induced by hypothalamic transplantation from genetically hypertensive to normotensive rats. J Neurosci 1991;ll:401-411.
81. Uchino K, Frohlich ED, Nishikimi T, et al. Spontaneously hypertensive rats demonstrate increased renal vascular α1-adrenergic receptor responsiveness. Am J Physiol 1991;260:889-893.
82. Clemow DB, Spitsbergen JM, McCarty R, et al. Altered NGF regulation may link a genetic predisposition for hypertension with hyperactive voiding. J Urol 1999;161:1372-1377.
83. Tarcan T, Azadzoi KM, Siroky MB, et al. Age-related erectile and voiding dysfunction: the role of arterial insufficiency. British Journal of Urology 1998;82(Suppll):26-33.
84. McVary KT. Erectile dysfunction and lower urinary tract symptoms secondary to BPH. European Urology 2005;47:838-845.
85. Yono M, Yamamoto Y, Yoshida M, et al. Effects of doxazosin on blood flow and mRNA expression of nitric oxide synthase in the spontaneously hypertensive rat genitourinary tract. Life Sci 2007;81:218-222.
86. Alvarez MA, Portilla L, Gonzalez IB, Ezcurra E: Insulin response to a short stress period. Psychoneuroendocrinology 1989; 14:241-244.
87. Raikkonen K, Keltikangas J, Hautanen A: The role of psychological coronary risk factors in insulin and glucose metabolism. J Psychosom Res 1994;38:705—713.
88.Reaven GM: Insulin resistance, the insulin resistance syndrome, and cardiovascular disease. Panmiverv Med 2005;47:201-210.
89. Dahle SE, Chokkalingam AP, Gao YT, et al. Body size and serum levels of insulin and leptin in relation to the risk of benign prostatic hyperplasia. J Urol 2002; 168:599-604.
90. Hammarsten J, Hogstedt B. Clinical, anthropometric, metabolic and insulin profile of men with fast annual growth rates of benign prostatic hyperplasia. Blood Pressure 1999;8:29-36.
91. Shieh SM, Sheu WH, Shen DC, et al. Glucose, insulin, and lipid metabolism in doxazosin-treated patients with hypertension. Am J Hypertens 1992;5:827-831.
92. Hautanen A. Synthesis and regulation of sex hormone-binding globulin in obesity. Int J Obes Relat Metab Disord 2000;24:64-70.
93. Peehl DM, Cohen P, Rosenfeld RG. The role of insulin-like growth factors in prostate biology. J Androl 1996; 17:2-4.
94. Toning N, Vinter-Jensen L, Pedersen SB, et al. Systemic administration of insulin-like growth factor I(IGF-I) causes growth of the rat prostate. J Urol1997;158:222-227.
95. Colao A, Marzullo P, Spiezia S, et al. Effect of growth hormone(GH) and insulin-like growth factor I on prostate diseases: an ultrasonographic and endocrine study in acromegaly, GH deficiency, and healthy subjects. J Clin Endocrinol Metab 1999;84:1986-1991.
96. Ketelslegers JM, Maiter D, Maes M, et al. Nutritional regulation of the growth hormone and insulin-like growth factor-binding proteins. Horm Res 1996;45:252-257.
97. Shpakov AO, Plesneva SA, Kuznetsova LA, Pertseva MN. Study of the functional organization of a novel adenylate cyclase signaling mechanism of insulin action. Biochemistry (Mosc) 2002;67:335-342.
98. Pertseva MN, Shpakov AO, Plesneva SA, Kuznetsova LA. A novel view on the mechanisms of action of insulin and other insulin superfamily peptides: involvement of adenylyl cyclase signaling system. Comp Biochem Physiol B Biochem Mol Biol 2003;134:11-36.
99. Ozden C, Ozdal OL, Urgancioglu G, et al. The correlation between metabolic syndrome and prostatic growth in patients with benign proatatic hyperplasia. Eur Urol 2007;51:199-206.
100.Yun AJ, Bazar KA, Lee PY, Gerber A, Daniel SM: The smoking gun: many conditions associated with tobacco exposure may be attributable to paradoxical compensatory autonomic responses to nicotine. Med Hypotheses 2005;64:1073-1079.
101. Untergasser G, Madersbacher S, Berger P. Benign prostatic hyperplasia: age-related tissue-remodeling. Exp Gerontol 2005;40:121-128.
102. Acosta S, Dizeyi N, Pierzynowski S, Aim P, Abrahamsson PA. Neuroendocrine cells and nerves in the prostate of the guinea pig: effects of peripheral denervation and castration. Prostate 2001;46:191-199.
103. Yun AJ, Lee PY, Bazar KA. Can thromboembolism be the result, rather than the inciting cause, of acute vascular events such as stroke, pulmonary embolism, mesenteric ischemia, and venous thrombosis? a maladaptation of the prehistoric trauma response. Med Hypotheses 2005 ;64:706-716.
104. Yun AJ, Lee PY, Bazar KA. Modulation of autonomic balance by tumors and viruses. Med Hypotheses 2004;63:344—351.
105. Nishimura M, Hashimoto T, Kobayashi H, et al. Association between cardiovascular autonomic neuropathy and left ventricular hypertrophy in diabetic hemodialysis patients. Nephrol Dial Transplant 2004;19:2532-2538.
106. Schneyer CA, Humphreys-Beher MG, Jirakulsomchok D, Hall HD. Effects of autonomic antagonists and growth factors on activity-mediated hyperplasia of rat parotid. Am J Physiol 1993;264:G763-766.
1.Purinton PT,Fletcher TF,Bradley WE.Gross and light microscopic features of the pelvic pleus in the rat.Anat Rec 1972;175:697-706.
2.McVary KT,Razzaq A,Lee C,Rademaker A,McKenna KE.Growth of the rat prostate gland is facilitated by the autonomic nervous system.Biol Reprod 1994;51:99-107.
3.Gosling JA.Autonomic innervation of the prostate;in Hinman F(ed):Benign Prostatic Hypertrophy.New York,Springer-Verlag,1983,pp349-360.
4.Wang JM,McKenna KE,Lee C.Determination of prostatic secretion in rats:effect of neurotransmitters and testosterone.The Prostate 1991;18:289-301.
5.Bruschini H,Schmidt RA,Tanagho EA.Neurologic control of prostatic secretion in the dog.Invest Urol 1978;15:288-290.
6.McVary KT,McKenna KE,Lee C.Prostate innervation.Prostate Suppl 1998;8:2-13.
7.Hoffman BB.Adrenoceptor-activating & other sympathomimetic drugs;in Katzung GB(ed):Basic & clinical pharmacology.8th edn.New York,McGraw-Hill Co,2001,pp 120-137.
8.Smith P,Rhodes NP,Beesley C,Ke Y,Foster CS.Prostatic stromal cell phenotype is diercetly modulated by norepinephrine.Urology 1998;51:663-670.
9.Collins MM,Stafford RS,O'Leary MP,Barry MJ.How common is prostatitis? A national survey of physician visits.J Urol 1998;159:1224-1228.
10.Wenninger K,Heiman JR,Rothman I,et al.Sickness impact of chronic nonbacterial prostatitis and its correlates.J Urol 1996;155:965-968.
11.彭轼平:良性前列腺增生概论.见:吴阶平主编;吴阶平泌尿外科学.济南,山东科学技术出版社,2004,1125-1139.
12.Wei JT,Calhoun E,Jacobsen SJ.Urologic Diseases in America project:benign prostatic hyperplasia.J Urol 2005;173:1256-1261.
13.Parkin DM,Bray F,Ferlay J,et al.Global cancer statistics,2002.CA Cancer J Clin 2005;55: 74-108.
14. American Cancer Society. Cancer Facts & Figures 2006. Atlanta: American Cancer Society; 2006.
15. Ferlay J, Bray F, Pisani P, et al. GLOBOCAN 2002 Cancer Incidence, Mortality and Prevalence Worldwide. IARC CancerBase No. 5, version 2. 0. IARCPress, Lyon, 2004.
16.Sidney S, Quesenberry CP Jr, Sadler MC, et al. Incidence of sugically treated benign prostatic hypertrophy and of prostate cancer among blacks and whites in a prepaid health care plan. Am J Epidemiol 1991;134:825-9.
17.Yun AJ, Doux JD. Opening the floodgates: Benign prostatic hyperplasia may represent another disease in the compendium of ailments caused by the global sympathetic bias that emerges with aging. Med Hypotheses 2006;67:392-394.
18.GassR. Benign prostatic hyperplasia: the opposite effects of alcohol and coffee intake. BJU Int 2002;90:649-654.
19.Corti R, Binggeli C, Sudano I, et al. Coffee acutely increases sympathetic nerve activity and blood pressure independently of caffeine content: role of habitual versus nonhabitual drinking. Circulation 2002; 106:2935-2940.
20.Shirao I, Tsuda A, Ida Y, et al. Effect of acute ethanol administration on noradrenaline metabolism in brain regions of stressed and nonstressed rats. Pharmacol Biochem Behav 1988;30:769-773.
21.Hawley RJ, Nemeroff CB, Bissette G, et al. Neurochemical correlates of sympathetic activition during severe alcohol withdrawal. Alcohol Clin Exp Res 1994;18:1312-1316.
22.Verbanck P, Seutin V, Massotte L, et al. Yohimbine can induce ethanol tolerance in an vitro preparation of rat locus coeruleus. Alcohol Clin Exp Res 1991;15:1036-1039.
23.Boyle P, Napvlkov P. The epidemiology of benign prostatic hyperplasia and observations on concomitant hypertension. Scand J Urol Nephrol Suppl 1995;68:7-12.
24.Hammarsten J, Hogstedt B. Hyperinsulinaemia as a risk factor for developing benign prostatic hyperplsia. Euro Urol 2001;39:151-158.
25.Michel MC, Heemann U, Schumacher H, Mehlburger L, Goepel M. Association of hypertension with symptoms of benign prostatic hyperplasia. J Urol 2004;172:1390-1393.
26.Claus S, Berges R, Senge T, et al. Cell kinetic in epithelium and stroma of benign prostatic hyperplasia. J Urol 1997;158:217-221.
27.Kyprianou N. Doxazosin and terazosin suppress prostate growth by inducing apoptosis: clinical significance. J Urol 2003;169:1520-1525.
28.Matityahou A, Rosenzweig N, Golomb E, et al. Rapid proliferation of prostatic epithelial cells in spontaneously hypertensive rats: A model of spontaneous hypertension and prostate hyperplasia. J Androl 2003;24:263-269.
29.Marinese D, Patel R, Walden PD, et al. Mechanistic investigation of the adrenergic induction of ventral prostate hyperplasia in mice. Prostate 2003;54:230-237.
30.Golomb E, Rosenzweig N, Eilam R, et al. Spontaneous hyperplasia of the ventral lobe of the prostate in aging genetically hypertensive rats. J Androl 2000,21:5 8-64.
31 .National Diabetes Information Clearinghouse(NDIC). National Diabetes Statistics. NIH Publication No. 06-3892. November 2005.
32.Krotkiewski M. Role of muscle capillarization and morphology in the development of insulin resistance and metabolic syndrome. Press Med 1994;23:1353-1356.
33.Ozden C, Ozdal OL, Urgancioglu G, et al. The correlation between metabolic syndrome and prostatic growth in patients with benign proatatic hyperplasia. Eur Urol 2007;51:199-206.
34.Dahle SE, Chokkalingam AP, Gao YT, et al. Body size and serum levels of insulin and leptin in relation to the risk of benign prostatic hyperplasia. J Urol 2002;168:599-604.
35. Hammarsten J, Hogstedt B. Clinical, anthropometric, metabolic and insulin profile of men with fast annual growth rates of benign prostatic hyperplasia. Blood Pressure 1999;8:29-36.
36.Landsberg L. Diet, obesity and hypertension: an hypothesis involving insulin, the sympathetic nervous system, and adaptive thermogenesis. Q J Med 1986;61:1081-1090.
37.Shieh SM, Sheu WH, Shen DC, et al. Glucose, insulin, and lipid metabolism in doxazosin-treated patients with hypertension. Am J Hypertens 1992;5:827-831.
38.McVary KT. Erectile dysfunction and lower urinary tract symptoms secondary to BPH. Eur Urol 2005;47:838-845.
39.Hautanen A. Synthesis and regulation of sex hormone-binding globulin in obesity. Int J Obes Relat Metab Disord 2000;24:64-70.
40.Peehl DM, Cohen P, Rosenfeld RG The role of insulin-like growth factors in prostate biology. J Androl 1996; 17:2-4.
41.Toning N, Vinter-Jensen L, Pedersen SB, et al. Systemic administration of insulin-like growth factor I(IGF-I) causes growth of the rat prostate. J Urol 1997; 158:222-227.
42.Colao A, Marzullo P, Spiezia S, et al. Effect of growth hormone(GH) and insulin-like growth factor I on prostate diseases: an ultrasonographic and endocrine study in acromegaly, GH deficiency, and healthy subjects. J Clin Endocrinol Metab 1999;84:1986-1991.
43. Shpakov AO, Plesneva SA, Kuznetsova LA, Pertseva MN. Study of the functional organization of a novel adenylate cyclase signaling mechanism of insulin action. Biochemistry (Mosc) 2002;67:335-342.
44. Pertseva MN, Shpakov AO, Plesneva SA, Kuznetsova LA. A novel view on the mechanisms of action of insulin and other insulin superfamily peptides: involvement of adenylyl cyclase signaling system. Comp Biochem Physiol B Biochem Mol Biol 2003; 134:11-36.
45.Nandeesha H, Koner BC, Dorairajan LN, et al. Hyperinsulinemia and dyslipidemia in non-diabetic benign prostatic hyperplasia. Clin Chim Acta 2006;370:89-93.
46.Rosen RC, Giuliano F, Carson CC. Sexual dysfunction and lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH). Eur Urol 2005;47:824-837.
47.Feldman HA, Goldstein I, Hatzichristou DG, et al. Impotence and its medical and psychosocial correlates: results of the Massachusetts Male Aging Study. J Urol 1994;151:54-61.
48.Nicolosi A, Glasser DB, Moreira ED, et al. Prevalence of erectile dysfunction and associated factors among men without concomitant diseases: a population study. Int J Impot Res 2003;15:253-257.
49.Rosen R, Altwein J, Boyle P, et al. Lower urinary tract symptoms and male sexual dysfunction: the multinational survey of the aging male(MSAM-7). Eur Urol 2003;44:637-649.
50. Hieble JP, Bylund DB, Clarke DE, et al. International Union of Pharmacology X. Recommendation for nomenclature of a1-adrenoceptors: Consensus update. Pharmacol Rev 1995;47:267-270.
51 .Hawrylyshyn KA, Michelotti GA, Coge F, et al. Update on human alpha1-adrenoceptor subtype signaling and genomic organization. Trends Pharmacol Sci 2004;25:449-455.
52. Price DT, Lefkowitz RJ, Caron MG, et al. Localization of mRNA for three distinct alpha 1-adrenergic receptor subtypes in human tissues: implications for human alpha-adrenergic physiology. Mol Pharmacol 1994; 45: 171-175.
53. Kojima Y, Sasaki S, Shinoura H, et al. Change of expression levels of alpha 1-adrenoceptor subtypes by administration of alphald-adrenoceptor-subtype-selective antagonist naftopidil in benign prostate hyperplasia patients. Prostate 2007;67:1285-1292.
54. Smith M, Schambra U, Wilson K, et al. Alpha 1-adrenergic receptors in human spinal cored: specific localized expression of mRNA encoding alpha 1-adrenergic receptor subtypes at four distinct levels. Mol Brain Res 1999;63:254-261.
55.Bouchelouche K, Andersen L, Alvarez S, et al. Increased contractile response to phenylephrine in detrusor of patients with bladder outlet obstruction: effect of the alphal A and alphal D-adrenergic receptor antagonist tamsulosin. J Urol 2005;173:657-661.
56.Souverein PC, Van Staa TP, Egberts AC, et al. Use of alpha-blcckers and the risk of hip/femur fractures. J Intern Med 2003;254:548-554.
57.Gotoh M, Kamihira O, Kinukawa T, et al. Comparision of tamsulosin and naftopidil for efficacy and safety in the treatment of benign prostatic hyperplasia: a randomized controlled trial. Br J Urol 2005;96:581-586.
58. Vaalasti A, Alho AM, Tainio H, et al. The effect of sympathetic denervation with 6-hydroxydopamine on the ventral prostate of the rat. Acta Histochem 1986;79:49-54.
59.Mayerhofer A, Bartke A, Steger RW. Catecholamine effects on testicular testosterone production in the gonadally active and the gonadally regressed adult golden hamster. Biol Reprod 1989;40:752-761.
60.Homma Y, Hamada K, Nakayama Y, et al. Effects of castration on contraction and alpha(1)-adrenoceptor expression in rat prostate. Br J Pharmacol 2000;131:1454-1460.
61.Farnsworth WE. Prostate stroma: physiology. Prostate 1999;38:60-72.
62.Slater M, Barden JA, Murphy CR. Changes in growth factor expression in the ageing prostate may disrupt epithelial-stromal homeostasis. Histochem J 2000;32: 357-364.
63.Foster CS. Pathology of benign prostatic hyperplasia. Prostate 2000; 45: 4 -14.
64.Yang G, Timme TL, Park SH, et al. Transforming growth factor betal transduced mouse prostate reconstitutions: I. Induction of neuronal phenotypes. Prostate 1997;33: 151-156.
65.Ghafar MA, Shabsigh A, Chichester P, et al. Effects of chronic partial outlet obstruction on blood flow and oxygenation of the rat bladder. J Urol 2002;167:1508-1512.
66.Clemow DB, Steers WD, McCarty R, et al. Altered regulation of bladder nerve growth factor and neurally mediated hyperactive voiding. Am J Physiol 1998;275:1279-1286.
67.Golomb E, Hill MR, Brown RG, et al. Ouabain enhances the mitogenic effect of serum in vascular smooth muscle cells. Am J Hypertens 1994;7:69-74.
68.Julius S. The evidence for a pathophysiology significance of the sympathetic overactivity in hypertension. Clin Exp Hypertens.1996;18:305-321.
69.Elima R, Malach R, Bergmann F, et al. Hypertension induced by hypothalamic transplantation from genetically hypertensive to normotensive rats. J Neurosci 1991;11:401-411.
70.Uchino K, Frohlich ED, Nishikimi T, et al. Spontaneously hypertensive rats demonstrate increased renal vascular α1-adrenergic receptor responsiveness. Am J Physiol 1991;260:889-893.
71.Golomb E, Kruglikova A, Dvir D, et al. Induction of atypical prostatic hyperplasia in rats by sympathomimetic stimulation. Prostate 1998;34:214-221.
72.Kyprianou N, Litvak JP, Borkowski A, et al. Induction of prostate apoptosis by doxazosin in benign prostatic hyperplasia. J Urol 1998; 159:1810-1815.
73.Clemow DB, Spitsbergen JM, McCarty R, et al. Altered NGF regulation may link a genetic predisposition for hypertension with hyperactive voiding. J Urol 1999;161:1372-1377.
74.McVary KT, Rademaker A, Lloyd GL, et al. Autonomic nervous system overactivity in men with lower urinary tract symptoms secondary to benign prostatic hyperplasia. J Urol 2005;174:1327-1333.
75.Ullich PM, Lutgendorf SK, Kreder KJ. Physiologic reactivity to a laboratory stress task among men with benign prostatic hyperplasia. Urology 2007;70:487-492.
76.Bjorntorp P. Body fat distribution, insulin resistance, and metabolic disease. Nutrition 1997; 13:795-803.
1.Lee CL, Kozlowski JM, Grayhack JT: Etiology of benign prostate hyperplasia. Urol Clin North Am 1995;22:237-246.
2.Lepor H: Alpha blockage for the treatment of benign prostatic hyperplasia. Urol Clin North Am 1995;22:375-386.
3.Chrousos GP, Gold PW: The concept of stress and stress system disorders. JAMA 1992;267:1244-1252.
4.Krieger JN: Classification, epidemiology and implications of chronic prostatitis in North America, Europe and Asia. Minerva Urol Nefrol 2004;56:99-104.
5.Badalyan RR, Fanarjyan SV, Aghajanyan IG: Chlamydial and ureaplasmal infections in patients with nonbacterial chronic prostatitis. Andrologia 2003;35:263-265.
6.Rudnick DH: Stress cause of prostatitis. Urology. 1985;26:320-1.
7.Gatenbeck L: Stress stimuli and the prostatic gland-an experimental study in the rat. Scand J Urol Nephrol Suppl. 1986;99:1-11.
8.McVary KT, Rademaker A, Lloyd GL, Gaan P: Autonomic nervous system overactivity in men with lower urinary tract symptoms secondary to benign prostatic hyperplasia. J Urol 2005;174:1327-1333.
9.Ullrich PM, Lutgendorf SK, Kreder KJ: Physiologic reactivity to a laboratory stress task among men with benign prostatic hyperplasia. Urology 2007;70:487-491.
10.Walsh PC, Retic AB, Stamey TA, Vaughan ED: Benign prostate hyperplasia;in Walsh PC, Retic AB, Stamey TA, Vaughan ED(eds): Campbell's Urology, 6th ed. Philadelphia, WB. Saunders,1992, pp 1014-1015.
11.Ozden C, Ozdal OL, Urgancioglu G, Koyuncu H, Gokkaya S, Memis A: The correlation between metabolic syndrome and prostatic growth in patients with benign prostatic hyperplasia. Eur Urol 2007;51:199-206.
12.Reaven GM: Insulin resistance, the insulin resistance syndrome, and cardiovascular disease. Panmiverv Med 2005;47:201-210.
13. Alvarez MA, Portilla L, Gonzalez IB, Ezcurra E: Insulin response to a short stress period. Psychoneuroendocrinology 1989;14:241—244.
14. Raikkonen K, Keltikangas J, Hautanen A: The role of psychological coronary risk factors in insulin and glucose metabolism. J Psychosom Res 1994;38:705—713.
15.McVary KT, McKenna KE, Lee C: Prostate innervation. Prostate 1998;8 (suppl):2-13.
16.Vaalasti A, Alho AM, Tainio H, Hervonen A: The effect of sympathetic denervation with 6-hydroxydopamine on the ventral prostate of the rat. Acta Histochem 1986;79:49-54.
17.Shibata Y, Kashiwagi B, Ono Y, Fukabori Y, Suzuki K, Honma S, Yamanaka H: The evaluation of rat prostate blood flow using a laser speckle flowmetry: a comparative study using the microsphere method in castrated and androgen-replenished rats. Urol Res 2004;32:44-8.
18.Wilson MJ, Woodson M, Wiehr C, Reddy A, Sinha AA: Matrix metalloproteinases in the pathogenesis of estradiol-induced nonbacterial prostatitis in the lateral prostate lobe of the Wistar rat. Exp Mol Pathol 2004;77:7-17.
19.Purinton PT, Fletcher TF, Bradley WE: Gross and light microscopic features of the pelvic pleus in the rat. Anat Rec 1972;175:697-706.
20.McVary KT, Razzaq A, Lee C, Rademaker A, McKenna KE: Growth of the rat prostate gland is facilitated by the autonomic nervous system. Biol Reprod 1994;51:99-107.
21.Gosling JA: Autonomic innervation of the prostate;in Hinman F(ed):Benign Prostatic Hypertrophy. New York, Springer-Verlag,1983,pp349-360.
22.Wang JM, McKenna KE, Lee C: Determination of prostatic secretion in rats: effect of neurotransmitters and testerone. Prostate 1991;18:289-301.
23.Jin Y, Chuan W, Ali Y: The plasma corticosterone in rats during physical and psychological stress. Acta Psychological Sinica 1991 ;4 :418-425.
24.Karp JD,Smith J, Hawk K: Restraint stress augments antibody production in cyclophosphamide treated mice. Physiol Behav Physico Behav 2000; 70: 271-278.
25. Schommer NC , Hellhammer DH, Kirschbaum C: Dissociation between reactivity of the hypothalamus - pituitary - adrenal axis and the sympathetic-adrenal-medullary system to repeated psychosocial stress. Psychosom Med 2003 ;65 :450 - 460.
26.Pei ZH, Zhu MZ, Pei JM, Gao Z, Lv SY: To detect the contents of mice plasma catecholamine by the high efficient liquid chromatography. Chin Heart 2003; 15:9-11.
27. Rosenzweig N, Horodniceanu J, Abramovici A: Phenylephrine-induced neurogenic prostatitis facilitates the promotion of PIN-like lesions in rats.Prostate 2004;59:107-113.
28.Golomb E, Rosenzweig N, Eilam R, Abramovici A: Spontaneous hyperplasia of the ventral lobe of the prostate in aging genetically hypertensive rats. J Androl 2000;21:58-64.
29.Boyle P, Napalkov P: The epidemiology of benign prostatic hyperplasia and observation on concomitant hypertension. Scand J Urol Nephrol 1995;168:7-12.
30.Gass R: Benign prostatic hyperplasia: the opposite effects of alcohol and coffee intake. BJU Int 2002;90:649-654.
31.Yun AJ, Bazar KA, Lee PY, Gerber A, Daniel SM: The smoking gun: many conditions associated with tobacco exposure may be attributable to paradoxical compensatory autonomic responses to nicotine. Med Hypotheses 2005;64:1073-1079.
32.Meigs JB, Mohr B, Barry MJ, Collins MM, McKinlay JB: Risk factors for clinical benign prostatic hyperplasia in a community-based population of healthy aging men. J Clin Epidemiol 2001;54:935-944.
1. Snider WD (1994) Functions of the neurotrophins during nervous system development: what the knockouts are teaching us. Cell 77:627-638
2.Paul AB, Grant ES, Habib FK (1996) The expression and localization of β-nerve growth factor (β-NGF) in benign and malignant human prostate tissue: relationship to neuroendocrine differentiation. Br J Cancer 74:1990-1996
3.Guan X-B, McKenna KE, McVary KT (1996) Expression of nerve growth factor in pelvic organs of male rat in response to denervation. Proc Am Urol Assoc Suppl 155:536
4.Li C, Watanabe G, Weng Q et al (2005) Expression of nerve growth factor (NGF), and its receptors trkA and p75 in the reproductive organs of the adult male rats. Zoolog Sci 22:933-937
5.Vaalasti A, Alho AM, Tainio H et al (1986) The effect of sympathetic denervation with 6-hydroxydopamine on the ventral prostate of the rat. Acta Histochem 79:49-54
6.Karp JD, Smith J, Hawk K (2000) Restraint stress augments antibody production in cyclophosphamide treated mice. Physiol Behav 70:271-8
7.Murphy RA, Watson AY, Rhodes JA (1984) Biological sources of nerve growth factor. Appl Neurophysiol 47:33-42
8.Djakiew D, Delsite R, Pflug B et al (1991) Regulation of growth by a nerve growth factor-like protein which modulates paracrine interactions between a neoplastic epithelial cell line and stromal cells of the human prostate. Cancer Res 51:3304-3310
9.Graham CW, Lynch JH, Djakiew D (1992) Distribution of nerve growth factor-like protein and nerve growth factor receptor in human prostatic hyperplasia and prostatic carcinoma. J Urol 147:1444-1447
10.Liu DT, Reid MT, Bridges DC et al (1996) Denervation, but not decentralization, reduces nerve growth factor content of the mesenteric artery. J Neurochem 66:2295-2299
11.Golomb E, Rosenzweig N, Eilam R et al (2000) Spontaneous hyperplasia of the ventral lobe of the prostate in aging genetically hypertensive rats. J Androl 21:58-64
12.Clemow DB, Steers WD, McCarty R et al (1998) Altered regulation of bladder nerve growth factor and neurally mediated hyperactive voiding. Am J Physiol 275:1279-1286
13.Kim JC, Park EY, Hong SH et al (2005) Changes of urinary nerve growth factor and prostaglandins in male patients with overactive bladder symptom. Int J Urol 12:875-880
14.Kim JC, Park EY, Seo SI et al (2006) Nerve growth factor and prostaglandins in the urine of female patients with overactive bladder. J Urol 175:1773-1776
15.Djakiew D (2000) Dysregulated expression of growth factors and their receptors in the development of prostate cancer. Prostate 42:150-160
16.Dalal R, Djakiew D (1997) Molecular characterization of neurotrophin expression and the corresponding tropomyosin receptor kinases (trks) in epithelial and stromal cells of the human prostate. Mol Cell Endocrinol 134:15-22
1.McVary KT, McKenna KE, Lee C: Prostate innervation. Prostate 1998;8 (suppl):2-13.
2.McVary KT, Razzaq A, Lee C, Rademaker A, McKenna KE: Growth of the rat prostate gland is facilitated by the autonomic nervous system. Biol Reprod 1994;51:99-107.
3.Beduschi MC, Beduschi R, Oesterling JE: Alpha-blockade therapy for benign prostatic hyperplasia: from a nonselective to a more selective alpha 1A-adrenergic antagonist. Urology 1998;51:861-872.
4.Owman C, Sjostrand NO: Short adrenergic neurons and catecholamine-containing cells in vas deferens and accessory male genital glands of different mammals. Z Zellforsch 1965;66:300-320.
5.Vaalasti A, Hervonen A: Autonomic innervation of the human prostate. Invest Urol 1980;17:293-297.
6.Vaalasti A, Hervonen A: Nerve endings in the human prostate. Am J Anat 1980;157:41-47.
7.Gosling JA: Autonomic innervation of the prostate;in Hinman F(ed):Benign Prostatic Hypertrophy. New York, Springer-Verlag,1983,pp349-360.
8.Lepor H, Shapiro E, Bowsher RR, Henry DP: Determination of norepinephrine levels in the adult human prostate. J Urol 1990; 144:1263-1266.
9.Tong YC, Hung YC, Lin SN, Cheng JT: The norepinephrine tissue concentration and neuropeptide Y immunoreactivity in genitourinary organs of the spontaneously hypertensive rat. J Auton Nerv Syst 1996;56:215-218.
10.Hieble JP, Bylund DB, Clarke DE, Eikenburg DC, Langer SZ, Lefkowitz RJ, Minneman KP, Ruffolo RR: International union of pharmacology X. Recommendation for nomenclature of alpha1-adrenoceptors: consensus update. Pharmacol. Rev. 1995; 47: 267-70.
11.Walden PD, Durkin MM, Lepor H, Wetzel JM, Gluchowski C, Gustafson EL: Localization of mRNA and receptor binding sites for the a1a-adrenoceptor subtype in the rat, monkey, and human urinary bladder and prostate. J Urol 1997;157:1032-1038.
12.Price DT, Schwinn DA, Lomasney JW, Allen LF, Caron MG, Lefkowitz RJ. Identification, quantification, and localization of mRNA for three distinct al adrenergic receptor subtypes in human prostate. J Urol 1993; 150:546-551.
13.Jacobs SC, Story MT: Exocrine secretion of epidermal growth factor by the rat prostate: Effect of adrenergic agents, cholinergic agents and vasoactive intestinal peptide. Prostate 1988; 13:79-87.
14.Smith P, Rhodes NP, Beesley C, Ke Y, Foster CS: Prostatic stromal cell phenotype is diercetly modulated by norepinephrine. Urology 1998;51:663-670.
15.Litvak JP, Borkowski A, Jacobs SC, Kyprianou N: Induction of prostate apoptosis by doxazosin: Targeting alpha 1 blockade in benign prostatic hyperplasia. J Urol 1997;157:279.
16.Golomb E, Rosenzweig N, Eilam R, Abramovici A: Spontaneous hyperplasia of the ventral lobe of the prostate in aging genetically hypertensive rats. J Androl 2000;21:58-64.
17.Clemow DB, Spitsbergen JM, McCarty R, Steers WD, Turtle JB: Altered NGF regulation may link a genetic predisposition for hypertension with hyperactive voiding. J Urol 1999; 161:1372-1377.
18.McVary KT, Rademaker A, Lloyd GL, Gaan P: Autonomic nervous system overactivity in men with lower urinary tract symptoms secondary to benign prostatic hyperplasia. J Urol 2005;174:1327-1333.
19.Ullrich PM, Lutgendorf SK, Kreder KJ: Physiologic reactivity to a laboratory stress task among men with benign prostatic hyperplasia. Urology 2007;70:487-491.
20.Marinese D, Patel R, Walden PD. Mechanistic investigation of the adrenergic induction of ventral prostate hyperplasia in mice. Prostate 2003;54:230-237.
21.Ghafar MA, Shabsigh A, Chichester P, Anastasiadis AG, Borow A, Levin RM, Buttyan R. Effects of chronic partial outlet obstruction on blood flow and oxygenation of the rat bladder. J Urol 2002;167:1508-1512.
22.Alvarez MA, Portilla L, Gonzalez IB, Ezcurra E: Insulin response to a short stress period. Psychoneuroendocrinology 1989;14:241—244.
23.Raikkonen K, Keltikangas J, Hautanen A: The role of psychological coronary risk factors in insulin and glucose metabolism. J Psychosom Res 1994;38:705-713.
24.Reaven GM: Insulin resistance, the insulin resistance syndrome, and cardiovascular disease. Panmiverv Med 2005;47:201-210.
25.Gass R: Benign prostatic hyperplasia: the opposite effects of alcohol and coffee intake. BJU Int 2002;90:649-654.
26.Yun AJ, Bazar KA, Lee PY, Gerber A, Daniel SM: The smoking gun: many conditions associated with tobacco exposure may be attributable to paradoxical compensatory autonomic responses to nicotine. Med Hypotheses 2005;64:1073-1079.
27.Meigs JB, Mohr B, Barry MJ, Collins MM, McKinlay JB: Risk factors for clinical benign prostatic hyperplasia in a community-based population of healthy aging men. J Clin Epidemiol 2001;54:935-944.