摘要
高血压病是我国常见病和引发心脑血管并发症最严重的疾病之一，中医药治疗高血压病已取得较大进展，但对中医药作用机制的研究尚需深入。夏膝口服液为导师黄永生教授治疗高血压肝肾失调、毒伤血络证的经验方，临床应用表明有较好的降压和改善临床症状的作用。前期的实验研究表明，本方能改善自发性高血压大鼠的血液流变学指标，改善血管内皮功能。本研究在前期研究的基础上，从中医学的整体观出发，从文献综述、理论研究及实验研究方面对其进行深入、系统地探讨。
文献综述
从古代和现代中医药对高血压病的病名、病因病机、证候学、证的客观化、中医药治疗等方面的研究情况进行了综述，并对当前在诊断及疗效评定标准、辨证分型和科研等方面存在的问题进行了述评和展望。
从现代医学角度对高血压病发病过程中的“神经内分泌免疫调节网络”进行研究，并据此对近年来关注较多的神经递质、细胞因子、内分泌系统及其在高血压病病理过程中的相互调节作用进行了综述，并进行了评述和展望。
理论研究
在归纳、整理古今文献的基础上，论述了肝肾阴阳失调是高血压病的发病基础，毒伤血络是高血压病的发病关键；论证了在高血压病的治疗中滋阴潜阳与解毒通络的内在联系。提出调整肝肾、解毒通络是治疗高血压病的有效途径，夏膝口服液就是在此理论指导下创立的。该方在立意上，体现了调整肝肾阴阳盛衰的主旨，在组方上昭示了以解毒通络为先的特点，为中医药治疗高血压病提供了新的研究思路。
实验研究
40只12周龄雄性SHR随机分为SHR空白组、夏膝口服液组、卡托普利组、厄贝沙坦组，每组10只，另取10只WKY大鼠作为正常对照组，给药8周观察下述指标。
1夏膝口服液对SHR心肾血管功能和结构的影响
1．1对SHR行为和一般状态的影响
研究表明夏膝口服液能改善SHR行为和一般状态，表明夏膝口服液对SHR中枢神经系统有一定的调理作用。
1．2对SHR血压的影响
夏膝口服液能抑制SHR血压随年龄增长而升高的趋势，给药4周后与空白组比较即有显著性差异(P＜0.05)，且降压效果平稳持久。
1．3对SHR左心室肥厚的影响
夏膝口服液能降低SHR左心室重量指数(LVWI)，与空白组比较有显著性差异(P＜0.01)，表明夏膝口服液能在一定程度上逆转左心室肥厚(LVH)。
1．4对靶器官损害的形态学观察：给药8周后，夏膝口服液能明显减轻SHR心肌细胞肥大，改善血管内膜状态，减轻肾脏间质纤维化，提示夏膝口服液能减轻靶器官损害。
2夏膝口服液对神经内分泌免疫调节网络的影响
2．1对儿茶酚胺的影响
采用酶联免疫吸附法(ELISA)测定SHR血浆儿茶酚胺(CA)浓度。结果表明，SHR血浆CA浓度显著高于WKY对照组(P＜0.01)；灌胃给予夏膝口服液20天即可显著降低大鼠血浆CA浓度(P＜0.01)，至第40天降至正常水平，与WKY对照组比较无显著性差异(P＞0.05)，并稳定维持至第60天。揭示CA浓度升高可能是SHR神经兴奋、肝阳上亢及血压升高的物质基础，夏膝口服液能通过降低CA浓度而发挥对SHR神经系统的调理作用，起到降低血压及改善大鼠行为状态的作用。
2．2对肿瘤坏死因子、细胞间粘附因子的影响
采用放射免疫法(RIA)测定SHR血清肿瘤坏死因子(TNF-α)含量，用免疫组化法(ICH)检测血管内皮细胞间粘附因子-1(ICAM-1)蛋白表达。结果显示夏膝口服液具有降低血清TNF-α浓度，调节血管内皮ICAM-1蛋白表达的作用。揭示TNF-α及ICAM-1的高表达所引起的内皮损伤，可能是毒伤血络的客观病理基础；夏膝口服液能在降压的同时，通过调整TNF-α及ICAM-1的表达而实现对SHR免疫机制紊乱的调节作用。
2．3对肾素-血管紧张素系统的影响
肾素-血管紧张素系统(RAS)对心血管系统发挥着循环和局部体液调节的作用，本研究采用放免法测定血浆肾素活性(PRA)、血浆和心肌局部血管紧张素Ⅱ(AngⅡ)含量，用分光光度计检测血管紧张素转换酶(ACE)活性，用免疫组化法(ICH)检测心肌血管紧张素Ⅱ受体1型(AT_1R)的蛋白表达，用逆转录聚合酶链反应(RT-PCR)检测AT1RmRNA基因表达的含量。结果表明夏膝口服液对SHR具有降低PRA、血浆和心肌局部AngⅡ含量、ACE活性的作用，并降低心肌AT_1R蛋白及基因表达。揭示夏膝口服液可通过抑制肾素-血管紧张素系统活性，发挥全身性调节的功能而降低SHR血压，具有类似血管紧张素转换酶抑制剂(ACEI)及血管紧张素受体拮抗剂(ARB)的降压机制。
结论
SHR存在神经内分泌免疫调节功能的异常，夏膝口服液能通过多组分、多途径、多环节、多靶向的特点降低SHR血压，逆转左心室肥厚，改善靶器官损害，使SHR神经内分泌免疫调控网络恢复正常。
In the present, hypertension has become one of the most common disease in China andhas often led to serious cardio-cerebral vascular complication. It has obtained great advancesin essential hypertension's treatment by Chinese medicine. While the function mechanism ofChinese medicine need to be further investigated. Xia xi Oral Liquid is a proved recipe forhypertension, which is worked out by the author's tutor Prof Huang Yong Sheng, deducingfrom the theory that the main mechanism of EH is the maladjustment of liver and kidney anddamage of superficial venues and lymph vessels. Clinical application has indicated that thisrecipe is quite effective in reducing blood pressure and improve clinical symptom. The furtherstudy indicates that the recipe could improve blood flowing deformation and ameliorateendothelium function of vascular in Spontaneously hypertensive rats (SHR).Based on furtherstudy, this article been performed from the aspects of reference review, theory study as well asexperiment on SHR to observe its effects on neuron-endocrine-immune network.
Reference review
The essay reviewed from the advances of such fields as followed: the ill-name, aetiologyand pathogenesis for EH, differential syndrome diagnosis, the substantial bases of thedifferential syndrome diagnosis, the treatment of the Chinese medicine, which is in ancientand modern times,moreover, included the evaluations and prospects on the criterions ofdiagnosis and curative effect as well as the problems lying in the selection of treatment basedon the differential syndrome diagnosis or scientific study. This essay summarized theexperimental study results and advances on the principle of neuron-endocrine-immunenetwdrk in EH according to such aspects as nervous intermediary, cell molecules, endocrinesystem and mutual regulation during the pathology process in EH. It also included evaluationsand prospects on these above.
Theory study
By inducing and sorting out the reference, we put forward the theory that the main bases of EH is the maladjustment of liver and kidney and the crux is the damage of superficialvenues and lymph vessels by poison, we expound and prove the inner link of adjustment ofliver and kidney and removing toxicity and obstruction, then put forward the theory that andremoving the toxicity and the obstruction is a valid path of treat Eli. Xia Xi Oral Liquid isoriginated from this theory which precipitating the point of adjustment of liver and kidney andthe characteristics of removing the toxicity and the obstruction, which provides theexperimental and theoretical bases for both its clinical application and its drug development.
Experimental study
40 12-week-old male SHR were divided randomly into SHR placebo group, Xia Xi OralLiquid control group, captopril control group and Irbesartanl control group, and 10 weightmatched male normotensive WKY rats were set as normal control(WKY group).Observe suchaspects as followed after administration 8 weeks.
1 The influence of Xia Xi Oral Liquid to the function and structure to cardiovascularsystem
1.1 behavior and general condition effect: Xia Xi Oral Liquid can improve the behavior andgeneral condition in SHR. That indicates that Xia Xi Oral Liquid has regulation function tocenter nervous system.
1.2 Decreasing blood effect: Xia Xi Oral Liquid can restrain the tendency that the blood willrise along with aging in SHR. It has a significant statistic sense between the Xia Xi OralLiquid treated group and the SHR placebo group after administration 4 weeks(P＜0.01). XiaXi Oral Liquid can maintain drug effect smooth and steady.
1.3 Reversing left ventricular hypertrophy(LVH) effect: Xia Xi Oral Liquid can reduce theratio of LVW to BW by 24.05%(P＜0.01), decrease the left ventricular mass index.. It has asignificant statistic sense between the Xia Xi Oral Liquid treated group and the SHR placebogroup (P＜0.01).Which indicates Xia Xi Oral Liquid can reverse LVH to a degree.
1.4 Morphology observation on target organ damages: Xia Xi Oral Liquid obviouslyalleviates the hypertrophy of cardiac muscle, protect blood vessel endothelium and reduce theproliferation of smooth muscle in tunica media after administration 8 weeks. The resultsshowed Xia Xi Oral Liquid has the function of protecting to cardiovascular system in SHR.
2 The influence of Xia Xi Oral Liquid to neuron-endocrine-immune network.
2.1 The influence of Xia Xi Oral Liquid to the density of catecholamine(CA) in plasma
Studying the density of CA in plasma in SHR with Enzyme-Linked ImmunosorbnentAssay (ELISA). The results showed that the density of plasma CA in SHR is obviously higherthan that in WKY rats(P＜0.01). Xia Xi Oral Liquid can reduce the lever of plasma CA inSHR, which had a significant statistic sense in comparing with placebo group afteradministration 20 days(P＜0.01),and can reduce the lever to normal standard after 40 days(P＜0.01), the tendency lasting for 60 days. The result showed that Xia Xi Oral Liquid has thefunction of reduce the density of CA in plasma in SHR. and increasing catecholaminestandard may be the inner basis for excitement, hyperactive liver-yang ascending andhypertension in SHR. Xia Xi Oral Liquid can depress the activity of sympathetic nerve, lowerblood pressure and improve behavior and general condition through reduce the density ofserum CA in SHR.
2.2 The influence of Xia Xi Oral Liquid to Tumor necrosis factor-α(TNF-α) density inplasma and intercellular adhesion molecule-1 (ICAM-1) expression in kidney arteriole in SHR
Studying the density of TNF-αin serum with radio-immunity(RIA)and ICAM-1expression in arteriole with immunohistochemistery (ICH). The results showed that Xia XiOral Liquid can reduce TNF-αdensity in serum and ICAM-1 expression in arteriole in SHR.The results revealed that the injury of endothelial cell induced by higher expression in TNF-αand ICAM-1 may be one of the pathology basis about damage of superficial venues andlymph vessels by poison. And XiaXi Oral Liquid can alleviate the injury of endothelial cellthrough reduce ICAM-1 expression in SHR so that educe the function of removing toxicityand obstruction.
2.3 The effect ofXia Xi Oral Liquid to rennin-angiotensin system (RAS)
Studying the plasma rennin activity(PRA) and plasma angiotensinⅡ(AngⅡ) ontent withradio-immunity, serum Angi0tensin-Converting enzyme (ACE)activity withspectrophotometer, angiotensinⅡreceptor typeⅠ(AT_1R) expression in cardiac muscle withimmunohistochemistery (ICH) and the gene expressive content of AT_1R in cardiac musclewith Reverse Transcription -polymerasechain reaction(RT-PCR)in rats. The results showedthat Xia Xi Oral Liquid can reduce PRA, AngⅡcontent, ACE activity, AT1R expression andthe gene expressive content of AT_1R in cardiac muscle. It revealed that Xia Xi Oral Liquid has the function of lower blood pressure as Angiotensin-Converting enzyme inhibitor(ACEI)andangiotensin receptor block(ARB).
Conclusion: SHR occur the abnormity of neuron-endocrine-immune network. Xia XiOral Liquid could lower blood pressure, reverse left ventricular hypertrophy, and improve targetorgan damages through a multiple composition, multiple pathways, multiple links andmultiple targets. Recover the function of neuron-endocrine-immune network.
引文
[1] 袁卫红，贺泽龙．高血压病的辨病辨证治疗思路探讨[J]．湖南中医药导报，2000．6(5)：10-11．
[2] 陈国庆．固本降压胺治疗高血压病112例[J]．陕西中医，2000，21(2)：54-55．
[3] 申志敏．梁贻俊从中医论治高血压病[J]．中国民康医学杂志，2006，18(2)：154-156．
[4] 杨建梅，王佑华．活血潜阳法治疗高血压病探讨[J]．中医研究，2006，19(1)：7-9．
[5] 郝现军，王冠民，李国臣．高血压病证治心得[J]．陕西中医学院学报，2006，(1)：27-29．
[6] 龚一萍．以肝为中心论治高血压(风眩)的理论探讨[J]．中医诊断学杂志，2000，6(1)：1-4．
[7] 张瑜．曹玉山治疗高血压病的经验[J]．甘肃中医，2005，18(10)：17-19．
[8] 门靖涫，祁芳珍．高血压从肾论治50例[J]．四川中医，2005，23(11)：40-41．
[9] 潘苏涌，高血压病的临床治疗[J]．光明中医，2005，20(6)：31-33．
[10] 邓旭光．高血压中医病机若干问题探讨[J]．中医杂志，2001，42(4)：197-199．
[11] 王锁欣．高血压病从脾论治疗效观察[J]．中医药学刊，2005，23(11)：23-25．
[12] 陈可冀．实用中西医结合内科治疗学[M]．第1版．北京：北京医科大学、中国协和医科大学联合出版社，1998：482-496．
[13] 张津平，高血压病中医治法探析[J]．天津中医药，2005，22(3)：220-222．
[14] 张晓天．心脑喜康对高血压病患者血压及相关神经肽的影响[J]．上海中医药大学学报，2000，14(2)：32-33．
[15] 李青鸟．原发性高血压病因之我见[J]．光明中医，2000，15(1)：8-10．
[16] 齐放．中医药防治高血压病研究进展[J]．北京中医杂志，2003，22(6)：1-3．
[17] 鞠大宏，韩学杰，谢雁鸣，等．高血压病从络论治探讨[J]．中国中医基础医学杂志，2001，7(9)：43-44．
[18] 李洪波，谢滨，黎秋明，等．调节气机升降为主治疗高血压病的临床研究[J]．辽宁中医杂志，2004，31(7)：569-570．
[19] 朱克俭，蔡光先．高血压病常见证候临床流行病学观察[J]．中国医药学报，1991，(1)：62-65．
[20] 朱克俭，蔡光先，卢六沙，等．高血压病证候及其转化规律研究[J]．中国中医药信息杂志，1999，6(2)：13-14．
[21] 蔡光先，朱克俭，韩育明，等．高血压病常见症候临床流行病学观察[J]．中医杂志，1999，40(8)：492-495．
[22] 周文泉，于向东，崔玲，等．高血压病证候和危险因素调查[J]．中国中西医结合杂志，2002，38(6)：324-326．
[23] 刘亦选，凌绍祥，刘小虹．1239例原发性高血压证候规律分析[J]．新中医，1993，(10)：20-22．
[24] 任敏之，符德玉，颜乾麟．高血压病患者中医证型与靶器官损害关系的临床研究[J]．四川中医，2006，24(9)：47-48．
[25] 黄春林．中医临床诊治丛书·心血管病专科．第1版[M]．北京：人民卫生出版社，2000：152-154．
[26] 中华人民共和国卫生部．中药新药临床研究指导原则(第二辑)[M]．北京：2002：28-32．
[27] 李泓，卜秦俐，胡宪蕴，等．原发性高血压肾素、血管紧张素Ⅱ、醛固酮及血浆心钠素水平与辨证分型关系[J]．中西医结合杂志，1991，(5)：271-273．
[28] 王宪衍，唐树德，王谷亮，等．原发性高血压患者中医分型与现代分型的关系[J]．上海第一医科大学学报．1998(1)：10-13．
[29] 吴辉，洗绍祥，黄衍寿．血管活性物质与原发性高血压中医证型的关系[J]．四川中医，2000，18(10)：11-13．
[30] 卢全生，雷燕，陈可冀．AT_1R基因多态性与原发性高血压中医证型及降压中药疗效的关系[J]．中国中西医结合杂志，2005，25(8)：682-686．
[31] 吴启锋，熊尚全，温茂详，等．高血压病中医证型与盐敏感性及胰岛素抵抗关系临床研究[J]．福建中医药，2002，33(3)：3-5．
[32] 沈毅，张继东，胡连海，等．原发性高血压病中医辨证分型与胰岛素抵抗的相关性研究[J]．山东大学学报(医学版)，2005，43(2)：34-36．
[33] 程志清，黄科．活血化瘀法治疗原发性高血压病的作用与地位[J]．浙江中医学院学报，2004，28(1)：2-4．
[34] 白春锦，周瀛，王丽，等．不同中医证型高血压患者的心血管危险因素分层、高血压分期、分级及血脂等指标变化特征[J]．中国临床康复，2006，23(9)：145-147．
[35] 程文立，乔占兵，陈郁生，等．原发性高血压患者红细胞流变学异常与血瘀证关系临床研究[J]．中国医药学报，2002，17(9)：563-566．
[36] 金国健，樊锦秀，张茂华．老年高血压中医证候分型的粘附分子表达与血微循环的关系[J]．浙江临床医学，2006，8(12)：1240-1241．
[37] 张臣，邢之华，刘卫平，等．不同中医证型高血压病血浆ET和血清NO的变化[J]．实用中医内科杂，2004，18(6)：508-509．
[38] 李玲，周淼．高血压病患者中医证型与血浆内皮素及胰岛素敏感指数关系的研究[J]．中医研究，2004，17(3)：28-29．
[39] 李小兵，洪永敦，冼绍祥．高血压病红细胞免疫和过氧化脂质与中医证候关系探讨[J]．辽宁中医杂志，2005，32(3)：177-178．
[40] 邓冰湘，谭达全．高血压病患者血压昼夜节律与靶器官损害及中医证型关系的研究[J]．湖南中医学院学报，2004，24(6)：48-49．
[41] 金益强，胡随瑜，鄢东红，等．高血压肝阳上亢证的分子机理研究[J]．中国中西医结合杂，2000，20(2)：87-89．
[42] 段开骏，刘洁，白春锦，等．不同中医辨证分型的高血压患者左心结构和功能指标变化[J]．中国临床康复，2006，10(3)：51-54．
[43] 姜奥．高血压病不同中医证型与心率变异相关性的研究[J]．中西医结合心脑血管病杂志．2005，3(1)：13-14．
[44] 赵奕，方文岩，赵治，等．高血压病中医辨证分型与基底动脉血流动力学探讨[J]．天津中医药，2005，22(4)：297-299．
[45] 罗伟，李保东，冯小平，等．高血压病虚实辨证与血浆ET、TXB2、6-K-PGFlα水平的关系[J]．中国中医基础医学杂志，1999，22(1)：1-4．
[46] 段开骏，刘洁，白春锦，等．不同中医辨证分型的高血压患者颈动脉血管重构变化[J]．中医药学刊，2006，24(5)：893-896．
[47] 刘国仗，马文君．高血压诊断和治疗研究治疗进展[J]．中华心血管杂志，2003，31(12)：884-886．
[48] 顾衡强，陈美华，邹襄谷，等．老年高血压颈动脉硬化多因素中医证型分析[J]．福建中医学院学报，2006，16(3)：7-10．
[49] 姚晓天，胡炜，程志清．高血压病影响因素与中医体质类型相关性研究[J]．中医药学刊．2004，22(12)：2314-2316．
[50] 陈利群，于海峰，王维谆．半夏白术天麻汤加味配合西药治疗痰浊上蒙型原发性高血压40例临床观察[J]．甘肃中医，2005，18(2)：1-2．
[51] 谭海彦，朱莉，邢之华，等．高血压病患者GSH-PX和CAT改变及天麻钩藤饮的干预作用[J]．中国中医急症，2005，14(3)：206-207．
[52] 陆新．杞菊地黄汤加减治疗肝肾阴虚型高血压病的临床研究[J]．新疆中医药，2004，22(5)：19-20．
[53] 王振东．加味黄精四草汤治疗高血压病35例[J]．现代中医药，2006，26(5)：3-5
[54] 李浩，刘芳，崔玲．降压胶囊治疗老年单纯收缩期高血压24例临床研究[J]．中医杂志，2004，45(1)：26-27．
[55] 谭元生，宋雪云，谭胜真．复方七芍降压片治疗高血压病的临床研究[J]．中成药，2005，27(7)：795-798．
[56] 李洪波，谢滨，黎秋明，等．调节气机升降为主治疗高血压病的临床研究[J]．辽宁中医杂志，2004，7(25)：12-13．
[57] 吴凯，何泮，廖蔚茜．化痰安神熄风法治疗原发性高血压的临床研究[J]．河北医学，2006．12(7)：635-637．
[58] 刘德桓，林惠琴，王秀宝，等．化瘀浊益肝肾法对原发性高血压患者生活质量的影 响随机双盲对照观察[J]．中国临床康复，2006，10(23)：9-12．
[59] 殷文慧，刘姣林，从虚辨证原发性高血压循证治疗53例疗效观察[J]．内蒙古医学杂志，2005，37(6)：536-537．
[60] 邢孝民，黄志华，房玉珍．平肝潜阳针法对原发性高血压患者甲襞微循环的影响[J]．中国临床康复，2005，9(7)：106-107．
[61] 王颖，童延清，刘舒音．降压汤泡脚治疗轻中度高血压的机理探讨[J]．中国社区医师，20068(130)：47-48．
[62] 陈华德．耳尖放血疗法改善高血压病肝阳上亢证[J]．中国社区医师，2006，22(312)：36-37．
[63] 严灿，高敏，邓中炎，等．高血压病左心室肥厚患者血浆P物质水平的变化及活血祛痰治法的影响[J]．中国中西医结合杂志，1998，18(6)：336-338．
[64] 魏爱英．水蛭土元粉联用硝苯吡啶治疗高血压并左室肥厚的临床研究[J]．中国中西医结合杂志，1996，16(4)：65-67．
[65] 胡小平，朱满芳，刘经磐，等．珍菊降压片与卡托普利对高血压左心室肥厚逆转作用的比较[J]．高血压杂志，1999，7(3)：42-44．
[66] 徐贵成，刘坤，潘立敏．降压舒心胶囊逆转高血压左心室肥厚的临床研究[J]．中西医结合心脑血管病杂志，2005，3(12)：1068-1170．
[67] 严冬，蒋卫民，唐蜀华，等．降压益肾颗粒治疗高血压病早期肾损害35例临床观察[J]．中医药研究，1999，15(1)：6-7．
[68] 郭铁标，李侠，郑德柱，等．加味防芪地黄汤治疗高血压肾损害所致肾功能不全疗效观察[J]．中国中医药信息杂志，2000，7(1)：49-51．
[1] 徐隆绍．神经内分泌学．第1版[M]．北京：中国医药科技出版社，1991．349～355．
[2] Besedovsky HO. Changes in blood hormones during the immune response [J]. Proc Soc Exp Biol Med,1988,15 (1):466～471.
[3] Fontana AF. Systhesis of IL-1 in the brain of endotoxin-treated mice [J].J Immunol,1990,13 (2):1610～1616.
[4] Dunn AJ. Cytokins as a bridge between immune and neuroendocrine systems [J]. Prog Neuroendocrinimmunol, 1990,3:26～34.
[5] Blalock JE. A molecular basic for bidirectional communication between the immune and neuroendocrine system [J]. Physiol Rev, 1989, 69 (1):1～5.
[6] Besedovsky HO, Sorkin E. Network of immunoneuroendocrine-interaction [J]. Clin Exp Immunol, 1991,27:5～12.
[7] 袁锦楣．临床神经免疫学．第1版[M]．北京：北京科学技术出版社，1992．258～267．
[8] 陈明哲．心脏病学，第一版[M]．北京：北京医科大学出版社．1999：771～774．
[9] Kuchel D. The autonomic nervous system and blood pressure regulation in human hyperte n sion. In: Genese J, et al. Hypertension:Physiopathology andTreatment. Second edition. NewYork[J]. Mc Graw-Hill Book Company, 1983:140～145.
[10] 陈修．心血管药理学，第二版[M]．北京：人民卫生出版社，1997：6～7．
[11] 汤健，唐朝枢，循环系统的内分泌功能[M]．北京：北京医科大学、中国协和医科大学联合出版社，1989：121～124．
[12] Mitchell KD, Braam B, andNavar G. Hypertensionogenic mechanisms mediated by renal actions of renin-angiotensin sssystem[J]. Hypertension, 1992,19 (1): 118～123.
[13] Mattiasson I, et at. Uptake and efflux of noradrenaline from piatelets:a model system for neurogenic mechanism in essential hypertension[J]. ClinSci, 1979,57 (1):225～229.
[14] 李佑福．高血压患者的血小板功能变化[J]．国外医学-生理病理科学与临床分册，1989．9(3)：68～71．
[15] 胡随瑜．中医肝病常见证型的植物神经功能状态研究[J]．湖南中医杂志，1996，12(1)：11～14．
[16] Fujinaga M, Scott J. Gene expression of catecholamine synthesizing enzymes and beta adrenoceptor subtypes during rat embryogenesis[J]. Neurosci Lett, 1997, 231 (2):108～112.
[17] 陈文彬．诊断学[M]．北京：人民卫生出版社，2001：434～435．
[18] 杨钢．内分泌生理与病理生理学[M]．天津：天津科学技术出版社，1994．301～305．
[19] 张桂福，邓宏明，罗佐杰，等．尿儿茶酚胺测定在嗜铬细胞瘤诊断中的价值[J]．广西医科大学学报，2002，19(4)：586-588．
[20] Braymetal A, KrushkaIJ, Li L, et al. Positional genomic analysis identifies thebeta (2)-adrenergic receptor gene as a susceptibility locus for human hypertension[J], Circulation,2000,101 (25) :2877-2882.
[21] Busjahn A, Li G, Faulhaber H, et al. Beta-2 adrenergic receptor gene variations, blood pressure, and heart size in normal twins[J].Hypertension,2000,35 (2):555-560.
[22] Hoit BD, Suresh DP, Craft L, et al. Beta-2 adrenergic receptor polymorphisms at amino acid 16 differentially influence agonist -stimulated blood pressure peripheral blood flow in normal individuals[J]. Am Heart J,2000,139 (3) :537-542.
[23] Krushkal J, Xiong M, Ferrell R, et al. Linkage and association of adrenergic and opamine receptor genes in the distal portion of the long arm of chromosome swith systolic blood pressure variation[J]. Hum Mol Genet,1998,7 (9):1379-1383.
[24] De Toledo FG, Thompson MA, Bolliger C, et al. x-Ⅰ.-DOPA in hib Ⅱs Na+phosphate cotransport across renal brush border membranes and increases renal excretion of phosphate[J]. Kidney Int,1999,55 (5):1833-1842.
[25] Perrichot R, Garcia-Ocana A, Couetts S, et al. Locally formed dopamine moduates renal Na=Pi co-transport through DA, and DA, receptors [J] BiochemJ, 1995, 312: 433-437.
[26] Grassi G, Catanmeno BM, Seravalle G, Lanfranchi A, Mancia G.Baroreflex control of sympathetic nerve activity in essential and secondary hypertension[J]. Hypertension, 1998,31: 68-7.
[27] Paran E, Neunamm L, Cristal N. Effects of mental and physical stress on plasma catecholamine levels before and afterp-adrenoceptor blocker treatment[J]. Eur J ClinP-harmacol,1992,43:11-15.
[28] Nielsen JR, Gram LF, Pederson PK. Plasma noradrenaline response to a multistage exercise test in young men at increased risk of developing essential hypertension[J]. Hypertension 1989, 7:377-382.
[29] Rahn KH, Barenbrock M, Hausberg M.The sympathetic nervous system in thepathogensis of hypertens[J]. J Hypertension,1999,17 (13):511-514.
[30] Knust U, Homuth V, Richter-Heinrich E, et al. A pilot study on the long-termefects of combined drug therapy and psychophysiologically-oriented therapy in patients with severe essential hypertension [J]. Wien Klin Wochenschr, 1991,103 (6): 163-168.
[31] Grassi G, Catanmeno BM, Seravalle G, Lanfranchi A, Mancia G. Baroreflex control of sympathetic nerve activity in essential and secondary hypertension[J]. Hypertension, 1998, 31: 68-71.
[32] 于汇民，王兵，刘国仗．原发性高血压的病因及发病机制[J]．新医学，2003，34(3)：135-136．
[33] 姜凤良．肿瘤坏死因子的研究进展[J]．医学综述，1999，5(7)：306-307．
[34] Ferrei N R. Zhao Y J, Takazawa H, et al. Turnor necrosis factor-a-angiotension interaction and regulation of blood press[J].Hypertens,1997,15:1481-1485.
[35] 王叔斐，许金成，芩治勋，等．高血压患者血清肿瘤坏死因子的检测及临床意义[J]．高血压杂志，1996，4(2)：134-136．
[36] 刘生祥，陈树兰，戴寿芝．高血压病与免疫球蛋白、肿瘤坏死因子及r-干扰素的关系[J]．中华心血管病杂志，1994，27(6)：422-425．
[37] 金惠铭，刘清行，张国平，等．TNF引起的微血管内皮细胞功能障碍及其分子机制[J]．中国病理生理杂志，2000，16(10)：940-943．
[38] 秦树存，王士雯．细胞因子与动脉硬化[J]．国外医学老年医学分册，1994，15(6)：193-196
[39] Ferrannini E, Buzzigoli G, Bonadonna R, et at. Insulin resistance in essential hypertension[J]. N Engl J Med, 1987,31 (7): 350-354.
[40] 王占科，许霖水．不同方式注射TNFa对正常小鼠胰岛素抵抗的影响[J]．基础医学与临床，1999，19(5)：87-89．
[41] 孙纳，田志刚，杨贵贞，等．TNFa对人胚胎胰岛分泌IL-6及对胰岛分泌功能的影响[J]．中国免疫学杂志，1998，14(4)：276-278．
[42] Rothlein R, Dustin ML Marlin SD, et al. A human intercellular adhesion molecule (ICAM-1) distinct from LFA-1[J]. Hypertension,1998,15: 481-485.
[43] Diamond MS, Staunton DE, Marlin SD, et al. Binding of integrin Mac-1 to the thi immunoglobin-like domain of ICAM-1 and its regulation[J]. Immunol, 1996, 37 (4) 270-274.
[44] Roebuck KA, Finnegan A Regulation of intercellular adhesion molecule-1 (CD54) gene expression[J]. Leukoc Biol, 1999; 66 (6): 876-878.
[45] O'Brien KD, Allen MD, McDonatd To, et al. Vascular cell adhesion molecule-1 is expressed in human coronary atherosclerotic plagues,implications for the mode of progression of advanced coronary atheroscterosis [J]. Clin Invest, 1993,92:945-951.
[46] Rothlein R, Mainolti EA, Czajkawski M, et al. Induction of oxidative stress by glutathione depletion cause severe hypertension in normal rats[J].Hypertension, 2000,36 (1):142-146.
[47] Leeuwenberg JF, Smeets EF, Neees JJ, et al. E-selectin and intercellcular adhesion molecule-1 are released by activated human endothelial cells in vitro[J].Immunology,1992,77 (4):543-549.
[48] Kiarash A, Pagano PJ, Taveh M, et al. U pregulated expression of rat heart intercellular adhesion molecule-1 in angiolensinⅡ bnt not phenylephrineinclne induce hypertension[J]. Hypertension,2001, 37 (1):58-65.
[49] Liu SQ, Moore M M, Glucksberg M R et al. Partial prevention of monocyte and ranulocyte activation in experimental vein grafts by using a biomechanical engineering approach[J]. J Biomech,1999, 32:1165-1169.
[50] Tropea BL, Huie P, Cooke JP, et al. hypertension enhanced monocyle adhesion in experimental atherosclerosis[J].J Vasc Surg, 1996, 23:596-601.
[51] Lubockaz H, Mnerovav U, Ellers H, et al. Grculating ICAM-1, ET-1, and VWF markers of endothelial dyfunction in umplicated essential hypertensiorn the effect of treatment with ACE in hibitors[J]. J Hun Hypertens 2002.16 (8):557-562.
[52] Kiarash A, Pagano PJ, Tayeh M, et al. Upregulated expression of rat heart intercellular adhesion molecule-1 in angiotensinⅡ but not phenylephrine-induced hypertension[J] Hypertension, 2001,7 (1) :58-65.
[53] 梁绪过，潘其兴．开博通与洛沙坦合用对冠心病患者血管内皮功能及可溶性细胞间粘附分子的作用[J]．中国综合临床，2002，18(8)：6888-6890．
[54] Warnholtz A, Nicheig G, Schulz E, et al. Increased NAOH-oxidaseomediated superoxide production in the early stages of atherosclerosis.Evidence for involvement of the renin-angiotensin system [J]. Circulation, 1999,100:2027-2033.
[55] Yamazaki T, Komuro I, Yazaki Y.Role of the Renin-Angiotensin System in Cardiac Hypertrophy.the American journal of cardiologyt[J], 1999,83 (12):53-58.
[56] Johnston C I, Risvanis J. Preclinical pharmacology of angiotensin Ⅱ receptor antagonists: Update andoutstanding issues[J]. Am J Hypertens, 1997,10 (122):306-10.
[57] Stephen G. Ball, MD, et al.Debate: Angiotensin-Converting Enzyme Inhibitors Versus Angiotensin Ⅱ Receptor Blockers-A Gap in Evidence-Based Medicine[J].the American journal of cardiology, 2003, 91 (10A) :14-18.
[58] Michael J. Mihma, b,l, Suvara K. et al. Effects of angiotensin Ⅱ on vascular endothelial cells:formation of receptor-mediated reactive nitrogen[J].species Biochemical Pharmacology, 2003, (65) 1189-1197.
[59] 冯惠清，王淑仙，戎惠萍，等．血管紧张素转换酶的临床检测研究[J]．河北职工医学院学报，2002，19(4)：40-43．
[60] Fuguo D, Tardif V, Cheniera I, et al. Angiotensin Ⅱ stimulates a novel angiotensin Ⅱ type lreceptor-associated protein, GLP gene expression in rat kidney proximal tubular cells[J]. Journal of Cardiothoracic-Renal Research,2006, 1 (1): 91-100.
[61] 刘力生．高血压[M]．北京：人民卫生出版社．2001：296-297．
[62] Guangyong Li, MS, a Ning Xi, et al. Investigation of angiotensinⅡ type 1 receptor by atomic force microscopy with functionalized tip[J]. Nanomedicine. 2005 , (1) : 306-312.
[63] Williams B .Angiotensin II and the Pathophysiology of Cardiovascular Remodel ing [J].The American journal of cardiologyt.2001,87 (8) : 10-16.
[64] Polizio AH , Pena C. Effects of angiotensin II type 1 receptor blockade on the oxidative stress in spontaneously hypertensive rat tissues[J].Regulatory Peptides,2005,12 (8) :1-5.
[65] Miyamoto A, Wada R, Inoue A,et al. Role of angiotensin II receptor subtypes in porcine basilar artery: Functional,radioligand binding, and cell culture studies[J]. Life Sciences ,2006,7 (8) : 943-949.
[66] Walter G. Thomas, Frederick, Mendelsohn.Angiotensin receptors: form and function and distribution[J]. The International Journal of Biochemistry & Cell Biology , 2003, (35) :774-779.
[67] Verheijen I, De Backer JP, Vanderheyden P,et al.A two-state model of antagonist-AT1 receptor interaction:further support by binding studies at low temperature[J].Biochemical Pharmacology , 2003, 65 (5) : 1339-1341.
[68] Okada H, Watanabe Y, Inoue T,et al.Angiotensin II type 1 receptor blockade attenuates renal fibrogenesis in an immune-mediated nephritic kidney through counter-activation of angiotensin II type 2 receptor[J]. Biochemical and Biophysical Research Communications, 2004,31 (4) : 403-408.
[69] Christopher ,Newton, Curran B,et al. Angiotensin II Type 1 Receptor Activation Increases Microvascular Permeability Via a Calcium Dependent Process[J]. Journal of Surgical Research, 2005,12 (3) : 33-39.
[70] Kubo T, Kinjyo N, Ikezawa A,et al.Spl decoy oligodeoxy nucleotide decreases angiotensin receptor expression and blood pressure in spontaneously hypertensive rats[J] .Brain Research, 2003,9 (92) : 1-8.
[71] Christopher R. Newton, M.D, Brian Curran,et al.Angiotensin II Type 2 Receptor Effect on Microvascular Hydraulic Permeability[J].Journal of Surgical Research , 2004,1 (20) ,83-88.
[72] Unger T, Culman J, Gohlke P. Angiotensin II receptorblockade and end-organ protection: Pharmacologicalrationale and evidence[J]. J Hypertens,1998,16(Suppl7):3-9.
[73] Kim D, Aizawa T, Wei H,et al.Angiotensin II increases hospho- diesterase 5A expression in vascular smooth muscle cells:A mechanism by which angiotensin Ⅱ antagonizes cGMP signaling[J]. Journal of Molecular and Cellular Cardiology , 2005,38 (10): 175-184.
[74] Walter G, Thomas, Qian H. Arresting angiotensin type 1 receptors[J]. Trends in Endocrinology and Metabolism, 2003, 14 (3): 243-249.
[75] Kubo T, Hagiwara Y.Enhanced activity of angiotensin Ⅱ-sensitive neurons in the anterior hypothalarnic area of spontaneously hypertensive rats[J].Brain Research , 2004,10 (20): 140-146.
[76] G. Jennings.New definitions in cardiovascular risk management: is it time for angiotensin Ⅱ receptor blockers to become first-line medication[J]. European Heart Journal Supplements, 2003, (5): 3-11.
[77] 鞠大宏，韩学杰，谢雁鸣，等．高血压病从络论治探讨[J]．中国中医基础医学杂志，2001．7(9)：43-45．
[78] Beverly H. Lorell.Role of Angiotensin AT1 and AT2 Receptors in Cardiac Hypertrophy and Disease[J]. the American journal of cardiologyt ,1999,83 (12): 42-46.
[1] 张笑丽，韩景辉，杨瑞霞，等．中医药治疗高血压病研究概况[J]．山西中医，2003，19(1)：53-54．
[2] 姜平．高血压病的基本病机与中药降压作用的研究[J]．甘肃中医学院学报，1996，13(3)：49-51．
[3] 丁爱国，汪翠红．肾虚血瘀与高血压病[J]．实用中西医结合杂志，1995，8(4)：211-213．
[4] 米勇锋，杨妹洁，孟婷．浅谈五脏与高血压[J]．陕西中医，2003，24(2)：148-149．
[5] 曲政军，汤钟娟．原发性高血压肝阳上亢证证治规律探讨．山东中医杂志．2003，22(4)：195-196．
[6] 黄力，史载祥．高血压病的病因病机和辫证论治[J]．中国临床医生．1999，27(12)：11-13．
[7] 梁硕名，梁思潜．高血压病与中药治疗[J]．中药材，1999，22(2)：96-97．
[8] 于汇民，王兵，刘国仗．原发性高血压的病因及发病机制学[J]．实用中西医结合杂志，2003，34(3)：135-137．
[9] 陈利国，尤可．中西医结合内科治疗学[M]．北京：人民卫生出版社，1999：95-104．
[10] 李学文．心血管疾病[M]．北京：科学技术出版社，1998：51-69．
[11] 陈敏章．中华内科学[M]．北京：人民卫生出版社，1999：1936-1953．
[12] 黄春林．心血管科专病中医临床诊治[M]．北京：人民卫生出版社，2000：129-131．
[13] 吴敦序．中医基础理论[M]．上海：上海科学技术出版社，1995：58-61．
[14] 常向明，姜杰．试论补虚当佐以行瘀滞[J]．贵阳中医学院学报，2002，24(1)：9-12．．
[15] 戴豪良，宋庆礼，陈泽霖．阴虚证35例临床病理学特征的分析[J]．中西医结合杂志，1989，9(1)：7-8．
[16] 胡庆福，陈泽霖，戴豪良．阴虚光剥舌形成机理的研究[J]．中西医结合杂志，1989，9(3)：153-155．
[17] 陈曙霞，常佩伦，郑新娟．陈旧性心肌梗塞患者血瘀、阴虚、阳虚型的若干指标观察[J]．中西医结合杂志，1989，9(11)：660-662．
[18] 李永莲．补肾需活血探析[J]．中医杂志，1996，37(10)：589-591．
[19] 徐勤．活血平肝益肾治疗高血压病55例疗效观察[J]．上海中医药杂志，1995，(7)：17-19．
[20] 李文艳．养肝熄风汤治疗原发性高血压病60例[J]．新中医，2001，33(1)：37-38．
[21] 袁肇凯．高血压病血瘀辨证与舌尖微观的初步研究[J]．中医杂志，1982，23(11)：65-67．
[22] 钱来森，周宏研，孙明．临界高血压患者血液流变学、血液动力学及心功能改变[J]．中华心血管杂志，1991，19(4)：225～227．
[23] 郑峰．高血压病中医辨证分析[J]．河北中医，2000，22(9)：651～653．
[24] 钱来森．高血压、血液流变学和心血管结构功能改变之间的关系[J]．国外医学．生理病理科学与临床分册，1990，10(2)：130-133．
[25] 龚兰生．原发性和肾性高血压循环血栓素β及6-酮-前列腺素F1α的改变[J]．中华心血管病杂志，1986；14(1)：31-34．
[26] 欧亚龙，彭素岚，徐应纤．高血压病与血瘀关系的试验研究[J]．四川中医，1991，(6)：4-6．
[27] 雷燕，黄启福，王永炎．论瘀毒阻络是络病形成的病理基础[J]．北京中医药大学学报，1999，22(2)：8～10．
[28] 刘燕明．现代经络研究的一点反思[J]．天津中医学院学报，2004，22(4)：8-10．
[29] 徐宗佩，张伯礼．“久病入络”患者舌象(舌底)观察与分析[J]．天津中医，1992，(4)：43-45．
[30] 朱克俭，蔡光先，卢六沙，等．高血压证候及其转化规律研究[J]，中国中医药信息杂志，1999．6(2)：13-15．
[31] 郭磊磊，周英，郑本德．高血压患者左心室重量指数与中医分型的关系[J]．浙江中医西医结合杂志，2002，12(4)：211-212．
[32] 张玲瑞，刘淑云，白智峰，等．原发性高血压和肾性高血压中医证候衍变规律及实质探讨[J]．中西医结合杂志，1992，(9)：18-21．
[33] Kim D, Aizawa T, Wei H,et al.Angi otensin Ⅱ increases hosphodiesterase 5A expression in vascular smooth muscle cells:A mechanism by which angiotensin Ⅱ antagonizes cGMP signaling[J]. Journal of Molecular and Cellular Cardiology,2005,38 (10): 175-184.
[34] 牛建昭．分子细胞学与疾病[M]，北京：人民卫生出版社，2003：468-472．
[35] 李小兵，方永奇，黄可儿．痰瘀证型的临床分析[J]．辽宁中医杂志，2000：27(2)：53-55．
[36] 陈银玲．从现代研究论“痰瘀同源”[J]．内蒙古中医药，1994；(2)：33-34．
[37] 陈颖，黄永生．降压1号对自发性高血压大鼠血压、血浆NO及ET的影响[J]．中国中医基础医学杂志，2006(5)：234-236．
[38] 刘真，于慧卿，魏运湘．夏枯草汤治疗高血压病及对血管内皮功能的影响[J]．陕西中医，2006，27(2) 162-164．
[39] 张莹霞．顽固性高血压40例中医疗效观察[J]．四川中医，2001，19(11)：23-24．
[40] 计倩文．清热活血汤治疗高血压病8例[J]．陕西中医，2002，23(8)：729-730．
[41] 江苏新医学院．中药大辞典[M]，第一版，上海：上海人民出版社，1977．1827-1828．
[42] 何云庆，李荣芷，冯腊枝，等．夏枯草化学成分的研究[J]．北京医科大学学报，1985，17(4)：297-299．
[43] 李宇航，牛欣，李玉谷，等．三草降压汤的降压作用探讨[J]．北京中医药大学学报，1996．19(1)：45-46．
[44] 王海波，张芝玉，苏中武，等．夏枯草总皂苷对麻醉大鼠急性心肌梗塞的保护作用及降压作用[J]．中草药，1994，25(8)：302-303．
[45] 冯培芳，秦南屏，方若莹，等．三物降压汤对自发性高血压大鼠血压及淋巴因子激活的杀伤细胞的影响[J]．中国循环杂志，1998，13(3)：178-180．
[46] 唐黎明．牛膝多糖药效学研究[J]．中成药，1996，18(5)：31-34．
[47] 李宗锴．牛膝多糖的免疫调节作用[J]．药学学报，1997，32(12)：881-883．
[48] 吕建新．牛膝多糖对人胸腔巨噬细胞的激活作用[J]．中国免疫学杂志，1999，15(9)：422-424．
[49] 邵树军，刘彩玉，刘雄伯，等．牛膝多糖对小鼠免疫功能影响的研究[J]．肿瘤防治杂志，2002，9(1)：57-59．
[50] 王宇学，宁勇，曹淑彦．牛膝多糖诱导单核细胞HLA-DR-αmRNA表达的实验研究[J]．湖北中医学院学报，2005，7(1)：39-41．
[51] 毛平，夏卉莉，袁秀荣，等．怀牛膝多糖抗凝血作用实验研究[J]．时珍国医国药，2000，11(12)：1075-1078．
[1] 赵光胜．现代高血压病学[M]．人民军医出版社，1999：308-309．
[2] 李剑，潘毅，严灿，等．滋补肝肾、活血祛痰方药对原发性高血压大鼠左心室肥厚的影响．山西中医[J]，2003，19(2)：54-56
[3] 王本祥．现代中药药理学[M]．天津科学技术出版社，1999：245-246．
[4] 刘力生，高血压[M]．北京：人民卫生出版社，2001：296-297．
[5] 许昌声，林志鸿，王华军．不同周龄的原发性高血压大鼠的血压和血管的反应性变化．中国实验动物学杂志[J]，1999，9(3)：176-178．
[6] Ruiz OM, Ruperez M, Esteban V, et al. Angiotensin Ⅱ: a key factor in the inflammatory and fibrotic response in kidney diseases [J]. Nephrol Dial Transplant, 2006,21 (1): 16-20.
[7] Ruperez M, Lorenzo O, Blanco□Colio LM, et al. The connective tissue growth factor is a mediator of angiotensin Ⅱ induced fibrosis[J]. Circulation, 2003,108 (12):1499-1509.
[8] Esteban V, Lorenzo O, Ruperez M, et al. Angiotensin Ⅱ, via AT1 and AT2 receptors and NF-kB pathway, regulates the inflammatory response in unilateral ureteral Obstruction [J]. J Am Soc Nephrol, 2004,15 (6): 1514-1529.
[9] 古萍，王庆．血浆儿茶酚胺对血液透析患者高血压的影响[J]．实用医学杂志，2004，44(3)：43-44．
[10] 邢艳霞，任慕兰，余卫平．妊娠高血压综合征尿儿茶酚胺变化及其与病变程度的关系[J]．中国实用妇科与产科杂志，2004，25(4)：52-53．
[11] 柳锋，郑智．丹参防治自发性高血压大鼠左室肥厚效应与对儿茶酚胺氧自由基代谢的影响[J]．中国急救医学，2003，22(11)：21-23．
[12] 王迪浔．人体病理生理学[M]．北京：人民卫生出版社，2002：832．
[13] 徐明，宋峣，冯新恒．不同交感-儿茶酚胺系统激活模式在心脏重塑中的作用[J]．中国分子心脏病学杂志，2007，7(1)：25-30．
[14] 孔剑琼，常桂娟，佐君丽．儿茶酚胺增多症对左心结构的影响[J]．中国循环杂志，2006，5(3)：42-45．
[15] Jing JL, Qiu YH, Peng YP. Immunoregulatory role of endogenous catecholamines synthesized by immune cells[J]. Acta Physiologica Sinica. 2006, 52(4): 21-29.
[16] 邱一华，彭聿平，王建军．儿茶酚胺调节免疫功能的细胞和分子机制[J]．生理科学进展，2003，22(4)：16-21
[17] 胡随瑜．中医肝病常见证型的植物神经功能状态研究[J]．湖南中医杂志，1996，12(1)：11-14．
[18] 朱崇学．肝火上炎证和肝胆湿热证患者血浆儿茶酚胺测定[J]．湖南医科大学学报，1996，21(4)：308-310．
[19] 金益强．中医肝病五类证候去甲肾上腺素和肾上腺素含量及诊断意义[J]．湖南医科大学学报，1997，22(1)：29-32．
[20] Badr K, Wainwright CL. Inflammation in the cardiovascular system: here, there and everywhere [J]. Curr Opin Pharmacol, 2004; 4:107-109.
[21] Lopez Jaramillo P. Calcium, nitric oxide, and preeclampsi [J]. Seminars Perinatol, 2000; 24:33-6.
[22] Cohen S,Bigazzr PE, Yoshida T. commentary.Similarities of T cell function in cell-mediated immunity and antibody production[J].Cell Immtmol, 1974;12:150-155.
[23] 姜凤良．肿瘤坏死因子的研究进展[J]．医学综述，1999；5(7)：306-307．
[24] 朱世明，李澄，朱兴雷．原发性高血压患者心脏损害与细胞因子的相关性研究[J]．山东医科大学学报，2001；39(1)：82-84．
[25] Bautista LE, Vera LM, Arenas IA, Gamarra G. Independent association between inflammatory markers (C-reactive protein, interleukin-6, and TNF-(α) and essential hypertension[J]. Hum Hypertens, 2005, 19:149-154.
[26] Barath P, Fishbcin MC, Cao J,et al. Tumor necrosis factor gene expression in humen vascular intimal smooth muscle cell detected by in situ hybridization [J].AmJPathol,1990;137 (3): 503-504.
[27] Yokoyama T, Nakano M, Bednarczyk JL, et al. Tumor necrosis factor-alpha provokes a hypertrophic growth response in adult cardiac myocytes [J]. Circu-lation, 1997;95 (5): 1247-1252.
[28] Bachem MG, Sellk-M, Melchior R,et al.Tumor necrosis factor alpha (TNF-α) and transforming growthfactorB1 (TGF-β_1) stimulate fibronectin synthesis and the transdifferentiation of fat-storing cells in rat liver into myofibroblasts [J]. Virchows ArchB,1993;63 (2):123-301.
[29] Landmesser U,Harrison DG.Oxidant stress as a marker for cardio-vascular events,ox marks the spot[J].Circulation. 2001,104(11);2638～2640.
[30] Touyz RM. Intracellular Mechanisms Involved in Vascular Remodeling of Resistance Arteries in Hypertension: Role of Angiotensin Ⅱ[J]. Exp Physiol, 2005, 12: (Epub ahead of print)
[31] Chae CU, Lee RT, Rifai N, Ridker PM. Blood pressure and inflammation in apparently healthy men [J].Hypertension, 2001;38:399-403.
[32] Bermudez EA, Rifai N, Buring J,Manson JE, Ridker PM.Inter relationships among circulating interleukin-6,C-reactive protein, and traditional cardio vascular risk factors in women[J]. Arterioscler Thromb Vasc Biol, 2002; 22:1668-1673.
[33] Kuwahara F, Kai H, Tokuda K, Takeya M, Takeshita A, Egashira K, et al. Hypertensive myocardial fibrosis and diastolicdys function: another model of inflammation[J]. Hypertension, 2004, 43:739-745.
[34] Virdis A,Schiffrin EL.Vascular inflammation: a role in vascular disease in hypertension [J]. Curt Opin Nephrol Hypertens 2003, 12:181-187.
[35] Sever PS, Dahlo fB, Poulter NR, Wedel H, Beevers G, Caulfield M, et al. Prevention of coronary and stroke events with atorvastatin in hypertensive patients who have average or lower-than-average cholesterol concentrations, in the Anglo-Scandinavian Cardiac Outcomes Trial-Lipid Lowering Arm(ASCOT-LLA): amulticentre randomized controlled trial[J]. Lancet, 2003, 361:1149-1158.
[36] Yamazaki T, Komuro I, Yazaki Y.Role of the Renin-Angiotensin System in Cardiac Hypertrophy.the American joumal of cardiologyt[J], 1999,83 (12):53-58.
[37] Johnston C I, Risvanis J. Preclinical pharmacology of angiotensin Ⅱ receptor antagonists: Update andoutstanding issues[J]. Am J Hypertens,1997,10 (122):306-10.
[38] 刘颖慧．血管紧张素受体拮抗剂逆转高血压左室肥厚的研究进展[J]．心血管康复医学杂志，2000，9(4)：96-98．
[39] 刘正湘，实用心血管受体学[M]．北京：科学出版社，2001：157．
[40] 费宇形，高连如，杨晔，等．原发性高血压患者血浆肾上腺髓质素水平变化意义的研究[J]．中国循环杂志，2001，16(6)：452-454．
[41] 李立新，王宇，张忠涛，等．血管紧张素Ⅱ受体拈抗剂抗纤维化及对Ⅰ型胶原基因表达影响的实验研究[J]．中华肝胆外科杂志，2004，10(1)：55-58．
[42] 胡亦新，李艳芳，郭广宏，等．依那普利和氯沙坦对自发性高血压大鼠同型半胱氨酸、环磷酸腺苷水平的影响[J]．中国老年学杂志，2005，25(5)：578～580．
[43] Okada H, Watanabe Y, Inoue T, et al.Angiotensin Ⅱ type 1 receptor blockade attenuates renal fibrogenesis in an immune-mediated nephritic kidney through counter-activation of angiotensin Ⅱ type 2 receptor[J]. Biochemical and Biophysical Research Communications, 2004,31(4): 403-408.
[44] Unger T, Culman J, Gohlke R Angiotensin Ⅱ receptorblockade and end-organ protection: Pharmacologicalrationale and evidence[J]. J Hypertens, 1998,16 (Suppl7): 3-9.
[45] Walter G, Thomas, Qian H. Arresting angiotensin type 1 receptors[J]. Trends in Endocrinology and Metabolism, 2003, 14 (3): 243-249.
[46] Kubo T, Hagiwara Y.Enhanced activity of angiotensin Ⅱ-sensitive neurons in the anterior hypothalamic area of spontaneously hypertensive rats[J].Brain Research, 2004,10 (20):140-146.
[47] Dahlof B, Left ventricular hypertrophy and angiotensin Ⅱ antagonists[J]. Am J Hypertens, 2001, 14 (12):174-178.
[48] Pueyo ME, Gonzalez W, Nicoletti A, Savoie F, Arnal JF, Michel JB. Angiotensin Ⅱ stimulates endothelial vascular cell adhesion molecule -1 via nuclear factor okappaB activation induced by intracellular oxidative stress[J].Arterioscler Thromb VascBiol, 2000, 20:645-651
[49] Hall JE, Hildebrant DA, Kuo J. Obesity hypertension: role of leptin and sympathetic nervous system[J]. Am J Hypertens, 2001,14 (6):1035～1039.
[50] 廖圣宝，丁荣光，丁丽俐，等．滋水降火饮对实验性高血压大鼠淋巴细胞Ang Ⅱ受体mRNA表达的影响[J]．中国中药杂志，2002，27(7)：531-532．