多沙唑嗪及其光学异构体对兔血压及尿道压的立体选择性
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摘要
良性前列腺增生(benign prostatic hyperplasia,BPH)可造成膀胱出口梗阻(bladder outlet obstruction,BOO),从而引起一系列的下尿路症状(lower urinary tract symptoms, LUTS)。α受体阻断药可阻断α受体,使膀胱颈部及前列腺平滑肌松弛,降低近段尿道压,已被广泛用于治疗BPH/LUTS。多沙唑嗪(racemic-doxazosin,rac-DOX)属选择性α1受体阻断药,是临床上治疗BPH的一线药物,但同时可引起心血管系统的不良反应。利用HPLC技术对rac-DOX进行手性拆分,可制备其单一光学异构体S-DOX和R-DOX。我们采用静脉给药法,观察rac-DOX及其光学异构体对麻醉兔颈总动脉血压和尿道压的影响,探讨rac-DOX及其光学异构体对下尿路药理作用的选择性。
目的:建立可同步测定血压和尿道压的动物模型,观察S-DOX、R-DOX和rac-DOX静脉给药对苯肾上腺素升高麻醉兔颈总动脉血压和尿道压的影响,分析rac-DOX及其光学异构体对下尿路药理作用的立体选择性。
方法:雄性新西兰白兔静脉注射乌拉坦(1.25g·kg-1)麻醉后,行气管插管,保持呼吸畅通;将聚乙烯导管插入左侧颈总动脉测定血压,导管另一端经压力换能器与八道生理记录仪相连,记录颈总动脉血压。于兔下腹部打开腹腔,剪开耻骨连合,暴露尿道。于膀胱顶部造一小口,将充满生理盐水的聚乙烯插管(外径1.3mm,内径0.8mm)经膀胱插入尿道,于膀胱颈部结扎固定,并于膀胱颈下方1cm处结扎尿道远端。聚乙烯管的另一端与压力换能器和八道生理记录仪相连,记录尿道压。手术完成后,经三通由聚乙烯管向尿道内注入一定量的生理盐水(0.2~0.4ml),使尿道压升至100cmH2O左右,平衡30min,待血压、尿道压稳定后开始实验。
结果:
1苯肾上腺素对麻醉兔颈总动脉血压的作用
静脉给予苯肾上腺素(1~45μg·kg-1),剂量依赖性升高麻醉兔颈总动脉收缩压、舒张压和平均动脉压;45μg·kg-1时升高收缩压、舒张压和平均动脉压的最大值分别为57.29±6.63、51.68±7.27和52.62±7.13(mmHg,n=8)。
2苯肾上腺素对麻醉兔尿道压的作用静脉给予苯肾上腺素(1~45μg·kg-1),剂量依赖性升高麻醉兔尿道压;45μg·kg-1时升高尿道压的最大值为51.75±9.72(cmH2O,n=8)。
3 rac-DOX、S-DOX及R-DOX对麻醉兔血压的影响静脉注射S-DOX、R-DOX和rac-DOX(0.5~50μg·kg-1),剂量依赖性降低麻醉兔颈总动脉收缩压、舒张压和平均动脉压;在50μg·kg-1剂量时,三者对平均动脉压的降低幅度分别为19.73±4.83%、23.80±8.45%和22.21±6.43%。R-DOX降低舒张压和平均动脉压的作用显著强于S-DOX(P<0.05)。
4 rac-DOX、S-DOX及R-DOX对苯肾上腺素升高麻醉兔血压和尿道压的影响
静脉给予S-DOX、R-DOX和rac-DOX(0.5~50μg·kg-1),均剂量依赖性降低苯肾上腺素升高麻醉兔颈总动脉收缩压、舒张压和平均动脉压的作用。S-DOX、R-DOX和rac-DOX在50μg·kg-1剂量时,降低苯肾上腺素升高平均动脉压的幅度分别为10.45±18.36%、53.38±11.86%和47.88±12.88%。S-DOX降低苯肾上腺素升高血压各参数的作用强度均显著弱于R-DOX和rac-DOX(P<0.01)。R-DOX降低苯肾上腺素升高血压各参数的作用强度与rac-DOX相同(P>0.05)。在尿道压方面,S-DOX、R-DOX和rac-DOX均能显著降低苯肾上腺素升高麻醉兔尿道压的作用;在50μg·kg-1剂量时,三者降低苯肾上腺素升高尿道压的幅度分别为48.18±15.85%、71.47±9.23%和53.26±15.35%;S-DOX的作用强度与rac-DOX相同(P>0.05),R-DOX的作用明显强于S-DOX与rac-DOX(P<0.01)。
采用尿道压抑制率与平均动脉压抑制率比值法计算药物抑制指数(IRIUP/IRMBP ratio),分析rac-DOX及其光学异构体在不同剂量下,降低苯肾上腺素升高麻醉兔平均动脉压和尿道压的选择性。S-DOX在各个剂量下IRIUP/IRMBP值均在2.5以上,而R-DOX和rac-DOX的IRIUP/IRMBP值均小于S-DOX。结果表明,S-DOX对下尿路的选择性高于R-DOX和rac-DOX。
结论:S-DOX静脉给药降低麻醉兔颈总动脉舒张压和平均动脉压的作用弱于R-DOX。S-DOX降低苯肾上腺素升高血压的作用显著弱于R-DOX和rac-DOX,而其降低苯肾上腺素升高尿道压的作用与rac-DOX相同。研究结果表明,S-DOX降低苯肾上腺素升高尿道压的选择性高于R-DOX和rac-DOX。
Benign prostatic hyperplasia (BPH) often leads to bladder outlet obstruction (BOO) and induces lower urinary tract symptoms (LUTS).α1-Adrenoceptor antagonists relax the smooth muscle of the bladder neck and prostate gland, and decrease the proximal urethral pressure by blockingα1-adrenoceptors. They were used most frequently for the treatment of BPH/LUTS. Racemic-doxazosin (rac-DOX), a highly selectiveα1-adrenoceptor antagonist, is considered as the first-line therapy for the patients with BPH and also produces several side effects in cardiovascular system. It was reported that S-doxazosin (S-DOX) and R-doxazosin (R-DOX) were prepared using chiral mobile phase HPLC. In the present experiments, we observed the effects of intravenous administration of S-DOX, R-DOX and rac-DOX on the carotid blood pressure and intra-urethral pressure (IUP) in the anesthetized rabbit to analyse the uroselectivity of doxazosin enantiomers.
Aim: To establish an animal model observing blood pressure and IUP at the same time in the anesthetized rabbit for evaluating the stereoselective effects of intravenous administration of S-DOX, R-DOX and rac-DOX between the carotid blood pressure and IUP.
Methods: New Zealand white male rabbit was anesthetized with an intravenous injection of urethane (1.25g·kg-1). Then, a catheter was inserted into trachea to allow drainage of bronchial secretion and to facilitate the breath. Polyethylene catheter was inserted into the left common carotid artery for blood pressure measurement. Blood pressure was monitored via the arterial catheter connected to a pressure transducer, and displayed on PowerLab/8sp through computer running the PowerLab Chart 5.0 software. The rabbit was opened through a midline incision over the lower abdomen. After resection of the pubic bone, the urethra was exposed. A small hole was made at the dome of the bladder in order to intubate a catheter (outer diameter 1.3mm, inner diameter 0.8mm) filled with physiological saline into the urethra from the bladder side. The catheter was fixed and secured at the bladder neck, and the distal end of urethra 1cm from the bladder neck was ligated. IUP was monitored via the catheter connected to a pressure transducer, and displayed on PowerLab/8sp through computer running the PowerLab Chart 5.0 software. After all the surgical preparations, the IUP was increased to approximately 100cmH2O by injection a small volume (0.2~0.4ml) of physiological saline into urethra via the catheter, then the blood pressure and IUP were equilibrated for 30min.
Results:
1 Effects of phenylephrine on the carotid blood pressure in anesthetized rabbits
Phenylephrine administered intravenously(1~45μg·kg-1) increased the systolic blood pressure (SBP), diastolic blood pressure (DBP) and mean arterial blood pressure (MBP) in the anesthetized rabbits in a dose-dependent manner. SBP, DBP and MBP were increased with phenylephrine at 45μg·kg-1 by 57.29±6.63, 51.68±7.27 and 52.62±7.13 (mmHg, n=8), respectively.
2 Effects of phenylephrine on the intra-urethral pressure in anesthetized rabbits
Phenylephrine administered intravenously(1~45μg·kg-1) increased the IUP in the anesthetized rabbits in a dose-dependent manner. IUP was increased with phenylephrine at 45μg·kg-1 by 51.75±9.72 (cmH2O, n=8).
3 Effects of doxazosin enantiomers on the boold pressure in anesthetized rabbits
S-DOX, R-DOX and rac-DOX administered intravenously (0.5~50μg·kg-1)decreased SBP, DBP and MBP in the anesthetized rabbits in a dose-dependent manner. The percentage inhibition of MBP by S-DOX, R-DOX and rac-DOX administered intravenously at 50μg·kg-1 was 19.73±4.83%, 23.80±8.45% and 22.21±6.43%, respectively. R-DOX had a stronger inhibitory effect on the DBP and MBP in comparison with S-DOX (P<0.05).
4 Effects of doxazosin enantiomers on phenylephrine-induced increases in blood pressure and intra-urethral pressure in anesthetized rabbits
S-DOX, R-DOX and rac-DOX administered intravenously (0.5~50μg·kg-1) decreased the increases of SBP, DBP and MBP induced by phenylephrine in the anesthetized rabbits in a dose-dependent manner. The percentage inhibition by S-DOX, R-DOX and rac-DOX on the increase in MBP induced by phenylephrine was 10.45±18.36%, 53.38±11.86% and 47.88±12.88%, respectively. S-DOX had a weaker inhibitory effect on phenylephrine-induced increase in SBP, DBP and MBP in comparison with R-DOX and rac-DOX (P<0.01). R-DOX inhibited the increase in the blood pressure induced by phenylephrine to the same extent as rac-DOX (P>0.05). S-DOX, R-DOX and rac-DOX decreased the increases in IUP induced by phenylephrine significantly. The percentage inhibition of the increase in IUP induced by phenylephrine by S-DOX, R-DOX and rac-DOX administered intravenously at 50μg·kg-1 was 48.18±15.85%, 71.47±9.23% and 53.26±15.35%. S-DOX inhibited the increase in the IUP induced by phenylephrine to the same extent as rac-DOX (P>0.05). R-DOX had a stronger inhibitory effect on phenylephrine-induced increase in IUP in comparison with S-DOX and rac-DOX (P<0.01).
The ratio of inhibition rate in IUP (IRIUP) to inhibition rate in MBP (IRMBP) by S-DOX, R-DOX and rac-DOX on the phenylephrine-induced responses was used to analyse the selectivity of an agent between blood pressure and bladder urinary system. The value (IRIUP/IRMBP ratio) of S-DOX at each concentration was larger than 2.5, but the values (IRIUP/IRMBP ratio) of R-DOX and rac-DOX were much smaller than S-DOX indicating that S-DOX had a higher uroselectivity than R-DOX and rac-DOX.
Conclusion: S-DOX administered intravenously decreases DBP and MBP more weakly than R-DOX in anesthetized rabbits. The inhibitory effect by S-DOX on the increase in blood pressure induced by phenylephrine is much weaker than that by R-DOX and rac-DOX, but the inhibitory effec by S-DOX on the increase in IUP induced by phenylephrine is the same to rac-DOX. Results of the present study suggest that S-DOX has chiral selectivity between cardiovascular system and urethral tissue much highly than R-DOX and rac-DOX in anesthetized rabbits.
目的:建立可同步测定血压和尿道压的动物模型,观察S-DOX、R-DOX和rac-DOX静脉给药对苯肾上腺素升高麻醉兔颈总动脉血压和尿道压的影响,分析rac-DOX及其光学异构体对下尿路药理作用的立体选择性。
方法:雄性新西兰白兔静脉注射乌拉坦(1.25g·kg-1)麻醉后,行气管插管,保持呼吸畅通;将聚乙烯导管插入左侧颈总动脉测定血压,导管另一端经压力换能器与八道生理记录仪相连,记录颈总动脉血压。于兔下腹部打开腹腔,剪开耻骨连合,暴露尿道。于膀胱顶部造一小口,将充满生理盐水的聚乙烯插管(外径1.3mm,内径0.8mm)经膀胱插入尿道,于膀胱颈部结扎固定,并于膀胱颈下方1cm处结扎尿道远端。聚乙烯管的另一端与压力换能器和八道生理记录仪相连,记录尿道压。手术完成后,经三通由聚乙烯管向尿道内注入一定量的生理盐水(0.2~0.4ml),使尿道压升至100cmH2O左右,平衡30min,待血压、尿道压稳定后开始实验。
结果:
1苯肾上腺素对麻醉兔颈总动脉血压的作用
静脉给予苯肾上腺素(1~45μg·kg-1),剂量依赖性升高麻醉兔颈总动脉收缩压、舒张压和平均动脉压;45μg·kg-1时升高收缩压、舒张压和平均动脉压的最大值分别为57.29±6.63、51.68±7.27和52.62±7.13(mmHg,n=8)。
2苯肾上腺素对麻醉兔尿道压的作用静脉给予苯肾上腺素(1~45μg·kg-1),剂量依赖性升高麻醉兔尿道压;45μg·kg-1时升高尿道压的最大值为51.75±9.72(cmH2O,n=8)。
3 rac-DOX、S-DOX及R-DOX对麻醉兔血压的影响静脉注射S-DOX、R-DOX和rac-DOX(0.5~50μg·kg-1),剂量依赖性降低麻醉兔颈总动脉收缩压、舒张压和平均动脉压;在50μg·kg-1剂量时,三者对平均动脉压的降低幅度分别为19.73±4.83%、23.80±8.45%和22.21±6.43%。R-DOX降低舒张压和平均动脉压的作用显著强于S-DOX(P<0.05)。
4 rac-DOX、S-DOX及R-DOX对苯肾上腺素升高麻醉兔血压和尿道压的影响
静脉给予S-DOX、R-DOX和rac-DOX(0.5~50μg·kg-1),均剂量依赖性降低苯肾上腺素升高麻醉兔颈总动脉收缩压、舒张压和平均动脉压的作用。S-DOX、R-DOX和rac-DOX在50μg·kg-1剂量时,降低苯肾上腺素升高平均动脉压的幅度分别为10.45±18.36%、53.38±11.86%和47.88±12.88%。S-DOX降低苯肾上腺素升高血压各参数的作用强度均显著弱于R-DOX和rac-DOX(P<0.01)。R-DOX降低苯肾上腺素升高血压各参数的作用强度与rac-DOX相同(P>0.05)。在尿道压方面,S-DOX、R-DOX和rac-DOX均能显著降低苯肾上腺素升高麻醉兔尿道压的作用;在50μg·kg-1剂量时,三者降低苯肾上腺素升高尿道压的幅度分别为48.18±15.85%、71.47±9.23%和53.26±15.35%;S-DOX的作用强度与rac-DOX相同(P>0.05),R-DOX的作用明显强于S-DOX与rac-DOX(P<0.01)。
采用尿道压抑制率与平均动脉压抑制率比值法计算药物抑制指数(IRIUP/IRMBP ratio),分析rac-DOX及其光学异构体在不同剂量下,降低苯肾上腺素升高麻醉兔平均动脉压和尿道压的选择性。S-DOX在各个剂量下IRIUP/IRMBP值均在2.5以上,而R-DOX和rac-DOX的IRIUP/IRMBP值均小于S-DOX。结果表明,S-DOX对下尿路的选择性高于R-DOX和rac-DOX。
结论:S-DOX静脉给药降低麻醉兔颈总动脉舒张压和平均动脉压的作用弱于R-DOX。S-DOX降低苯肾上腺素升高血压的作用显著弱于R-DOX和rac-DOX,而其降低苯肾上腺素升高尿道压的作用与rac-DOX相同。研究结果表明,S-DOX降低苯肾上腺素升高尿道压的选择性高于R-DOX和rac-DOX。
Benign prostatic hyperplasia (BPH) often leads to bladder outlet obstruction (BOO) and induces lower urinary tract symptoms (LUTS).α1-Adrenoceptor antagonists relax the smooth muscle of the bladder neck and prostate gland, and decrease the proximal urethral pressure by blockingα1-adrenoceptors. They were used most frequently for the treatment of BPH/LUTS. Racemic-doxazosin (rac-DOX), a highly selectiveα1-adrenoceptor antagonist, is considered as the first-line therapy for the patients with BPH and also produces several side effects in cardiovascular system. It was reported that S-doxazosin (S-DOX) and R-doxazosin (R-DOX) were prepared using chiral mobile phase HPLC. In the present experiments, we observed the effects of intravenous administration of S-DOX, R-DOX and rac-DOX on the carotid blood pressure and intra-urethral pressure (IUP) in the anesthetized rabbit to analyse the uroselectivity of doxazosin enantiomers.
Aim: To establish an animal model observing blood pressure and IUP at the same time in the anesthetized rabbit for evaluating the stereoselective effects of intravenous administration of S-DOX, R-DOX and rac-DOX between the carotid blood pressure and IUP.
Methods: New Zealand white male rabbit was anesthetized with an intravenous injection of urethane (1.25g·kg-1). Then, a catheter was inserted into trachea to allow drainage of bronchial secretion and to facilitate the breath. Polyethylene catheter was inserted into the left common carotid artery for blood pressure measurement. Blood pressure was monitored via the arterial catheter connected to a pressure transducer, and displayed on PowerLab/8sp through computer running the PowerLab Chart 5.0 software. The rabbit was opened through a midline incision over the lower abdomen. After resection of the pubic bone, the urethra was exposed. A small hole was made at the dome of the bladder in order to intubate a catheter (outer diameter 1.3mm, inner diameter 0.8mm) filled with physiological saline into the urethra from the bladder side. The catheter was fixed and secured at the bladder neck, and the distal end of urethra 1cm from the bladder neck was ligated. IUP was monitored via the catheter connected to a pressure transducer, and displayed on PowerLab/8sp through computer running the PowerLab Chart 5.0 software. After all the surgical preparations, the IUP was increased to approximately 100cmH2O by injection a small volume (0.2~0.4ml) of physiological saline into urethra via the catheter, then the blood pressure and IUP were equilibrated for 30min.
Results:
1 Effects of phenylephrine on the carotid blood pressure in anesthetized rabbits
Phenylephrine administered intravenously(1~45μg·kg-1) increased the systolic blood pressure (SBP), diastolic blood pressure (DBP) and mean arterial blood pressure (MBP) in the anesthetized rabbits in a dose-dependent manner. SBP, DBP and MBP were increased with phenylephrine at 45μg·kg-1 by 57.29±6.63, 51.68±7.27 and 52.62±7.13 (mmHg, n=8), respectively.
2 Effects of phenylephrine on the intra-urethral pressure in anesthetized rabbits
Phenylephrine administered intravenously(1~45μg·kg-1) increased the IUP in the anesthetized rabbits in a dose-dependent manner. IUP was increased with phenylephrine at 45μg·kg-1 by 51.75±9.72 (cmH2O, n=8).
3 Effects of doxazosin enantiomers on the boold pressure in anesthetized rabbits
S-DOX, R-DOX and rac-DOX administered intravenously (0.5~50μg·kg-1)decreased SBP, DBP and MBP in the anesthetized rabbits in a dose-dependent manner. The percentage inhibition of MBP by S-DOX, R-DOX and rac-DOX administered intravenously at 50μg·kg-1 was 19.73±4.83%, 23.80±8.45% and 22.21±6.43%, respectively. R-DOX had a stronger inhibitory effect on the DBP and MBP in comparison with S-DOX (P<0.05).
4 Effects of doxazosin enantiomers on phenylephrine-induced increases in blood pressure and intra-urethral pressure in anesthetized rabbits
S-DOX, R-DOX and rac-DOX administered intravenously (0.5~50μg·kg-1) decreased the increases of SBP, DBP and MBP induced by phenylephrine in the anesthetized rabbits in a dose-dependent manner. The percentage inhibition by S-DOX, R-DOX and rac-DOX on the increase in MBP induced by phenylephrine was 10.45±18.36%, 53.38±11.86% and 47.88±12.88%, respectively. S-DOX had a weaker inhibitory effect on phenylephrine-induced increase in SBP, DBP and MBP in comparison with R-DOX and rac-DOX (P<0.01). R-DOX inhibited the increase in the blood pressure induced by phenylephrine to the same extent as rac-DOX (P>0.05). S-DOX, R-DOX and rac-DOX decreased the increases in IUP induced by phenylephrine significantly. The percentage inhibition of the increase in IUP induced by phenylephrine by S-DOX, R-DOX and rac-DOX administered intravenously at 50μg·kg-1 was 48.18±15.85%, 71.47±9.23% and 53.26±15.35%. S-DOX inhibited the increase in the IUP induced by phenylephrine to the same extent as rac-DOX (P>0.05). R-DOX had a stronger inhibitory effect on phenylephrine-induced increase in IUP in comparison with S-DOX and rac-DOX (P<0.01).
The ratio of inhibition rate in IUP (IRIUP) to inhibition rate in MBP (IRMBP) by S-DOX, R-DOX and rac-DOX on the phenylephrine-induced responses was used to analyse the selectivity of an agent between blood pressure and bladder urinary system. The value (IRIUP/IRMBP ratio) of S-DOX at each concentration was larger than 2.5, but the values (IRIUP/IRMBP ratio) of R-DOX and rac-DOX were much smaller than S-DOX indicating that S-DOX had a higher uroselectivity than R-DOX and rac-DOX.
Conclusion: S-DOX administered intravenously decreases DBP and MBP more weakly than R-DOX in anesthetized rabbits. The inhibitory effect by S-DOX on the increase in blood pressure induced by phenylephrine is much weaker than that by R-DOX and rac-DOX, but the inhibitory effec by S-DOX on the increase in IUP induced by phenylephrine is the same to rac-DOX. Results of the present study suggest that S-DOX has chiral selectivity between cardiovascular system and urethral tissue much highly than R-DOX and rac-DOX in anesthetized rabbits.
引文
1 Kumar VL, Dewan S. Alpha adrenergic blockers in the treatment of benign hyperplasia of the prostate. Int Urol Nephrol, 2000, 32(1):67~71
2 顾方六, 主编. 现代前列腺病学. 人民军医出版社, 2003, 164~167
3 Owens PK, Fell AF, Coleman MW, et al. Chiral recognition in liquid chromatography utilizing chargeable cyclodextrins for resolution of doxazosin enantiomers. Chirality, 1997, 9 (2):184~190
4 Niu CQ, Ren LM. Chiral separation of three new antagonists of alpha-1 adrenoceptors by capillary electrophoresis. Acta Pharm Sin (药学学报), 2000, 35(6):451~453
5 Niu CQ, Ren LM. Chiral separation and preparation of three new antagonists of α1 adrenoceptors by chiral mobile phase HPLC. Acta Pharm Sin (药学学报), 2002, 37(6):450~453
6 Ma SP, Ren LM, Zhao D, et al. Chiral selective effects of doxazosin enantiomers on blood pressure and urinary bladder pressure in anesthetized rats. Acta Pharmacol Sin,2006, 27(11):1423~1430
7 田河林, 任雷鸣, 何东伟. 多沙唑嗪对映体对大鼠血压和排尿功能的影响. 中国药理学通报, 2007, 23(2):240~246
8 田河林, 任雷鸣. 多沙唑嗪对映体不同给药途径对豚鼠膀胱排尿功能的影响. 中国药理学与毒理学杂志, 2007, 21(2):118~123
9 金锡御, 吴雄飞, 主编. 尿道外科学. 人民卫生出版社, 2004, 55~59
10 Yamaguchi T, Nagano M, Osada Y. Effects of different alpha-1 adrenoceptor blockers on proximal urethral function using in vivo isovolumetric pressure changes. J Smooth Muscle Res, 2005, 41(5):247~256
11 Hattori Y, Kanno M. Role of α1-adrenoceptor subtypes in production of the positive inotropic effects in mammalian myocardium implications for the α1-adrenoceptor subtype distribution. Life Sci, 1998, 62 (17-18):1449~1453
12 严干新, 汤树本, 张海燕. 苯肾上腺素对豚鼠和兔离体心室乳头肌的作用. 生理学报, 1986, 38(6):619~626
13 Satoh M, Enomoto K, Niwano H, et al. Regional differences in α 1-adrenoceptor subtypes in rabbit arteries. Eur J Pharmacol, 1998, 350(1):67~73
14 Satoh M, Enomoto K, Takayanagi I, et al. Analysis of α 1-adrenoceptor subtypes in rabbit aorta and arteries: regional difference and co-existence. Eur J Pharmacol, 1999, 374(2):229~240
15 孙则禹. 肾上腺素能受体与下尿路症状. 江苏医药, 2005, 31(3):214~215
1 Kirby RS, Andersen M, Gratzke P, et al. A combined analysis of double-blind trial of the efficacy and tolerability of doxazosin-gastrointestinal therapeutic system, doxazosin, standard and placebo in patients with BPH. BJU Int, 2001, 87(3):192~200
2 潘启超. 新α1受体阻断剂-多沙唑嗪的药理及临床(一). 广州医药, 1999, 30(5):6~7
3 卢竟前, 曹晶茗. 多沙唑嗪应用于心血管病的研究进展. 现代中西医结合杂志. 2005, 14(9):1242~1244
4 MacDonald R, Wilt TJ, Howe RW. Doxazosin for treating lower tract symptoms compatible with benign prostatic obstruction:a systematic review of efficacy and adverse effects. BJU Int, 2004, 94(9):1263~1270
5 Owens PK, Fell AF, Coleman MW, et al. Chiral recognition in liquid chromatography utilizing chargeable cyclodextrins for resolution of doxazosin enantiomers. Chirality, 1997, 9(2):184~190
6 Niu CQ, Ren LM. Chiral separation of three new antagonists of alpha-1 adrenoceptors by capillary electrophoresis. Acta Pharm Sin(药学学报), 2000, 35(6):451~453
7 Niu CQ, Ren LM. Chiral separation and preparation of threenew antagonists of α1 adrenoceptors by chiral mobile phase HPLC. Acta Pharm Sin(药学学报), 2002, 37(6):450~453
8 Ma SP, Ren LM, Zhao D, et al. Chiral selective effects of doxazosin enantiomers on blood pressure and urinary bladder pressure in anesthetized rats. Acta Pharmac Sin, 2006, 27(11):1423~1430
9 田河林, 任雷鸣, 何东伟. 多沙唑嗪对映体对大鼠血压和排尿功能的影响. 中国药理学通报, 2007, 23(2):240~246
10 田河林, 任雷鸣. 多沙唑嗪对映体不同给药途径对豚鼠膀胱排尿功能的影响. 中国药理学与毒理学杂志, 2007, 21(2):118~123
11 Yamaguchi T, Nagano M, Osada Y. Effects of different alpha-1 adrenoceptor blockers on proximal urethral function using in vivo isovolumetric pressure changes. J Smooth Muscle Res, 2005, 41(5):247~256
12 孙则禹. 肾上腺素能受体与下尿路症状. 江苏医药, 2005, 31(3):214~215
13 Sica DA. Doxazosin and congestive heart failure. Congest Heart Fail, 2002, 8(3):178~184
14 Hatano A, Tang R, Walden PD, et al. The α-adrenoceptor antagonist properties of the enantiomers of doxazosin in human prostate. Eur J Pharmacol, 1996, 313(1-2):135~143
15 卢海刚, 赵丁, 任雷鸣. 多沙唑嗪对映体对兔离体膀胱逼尿肌的作用和作用机制. 中国药理学通报, 2008, 24(4):513~517
16 Niu CQ, Zhao D, Jia XM, et al. α1-Adrenoceptor antagonist profile of doxazosin and its enantiomers in isolated rabbit blood vessels. Chin J Pharmacol Toxical (中国药理学与毒理学杂志), 2003, 17(5):354~359
17 卢海刚, 刘丽芳, 任雷鸣. 多沙唑嗪对映体对兔四种血管α受体的作用. 药学学报, 2007, 42(2):145~151
1 Harada T, Kumazaki T, Kigure T, et al. Effect of adrenergic agents on urethral pressure and urethral compliance measurements in dog proximal urethra. J Urol, 1989, 142:189~192
2 Kontani H, Nakagawa M, Sakai T. Effects of adrenergic agonists on an experimental urinary incontinence model in anesthetized rabbits. Jap J Pharmacol. 1992, 58:339~346
3 Yoshimura N, Mizuta E, Kuno S, et al. The dopamine D1 receptor agonist SKF 38393 suppresses detrusor hyperreflexia in the monkey with parkinsonism induced by 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP). Neuropharmacology, 1993, 32:315~321
4 Danuser H, Thor KB. Spinal 5-HT2 receptor-mediated facilitation of pudendal nerve reflexes in the anaesthetized cat. Br J Pharmacol, 1996, 118:150~154
5 Ghoniem GM, Shoukry MS, Monga M. Effects of anesthesia on urodynamic studies in the primate model. J Urol, 1996, 156:233~236
6 Watanabe T, Perkash I, Constantinou CE. Modulation of detrusor contraction strength and micturition characteristics by intrathecal baclofen in anesthetized rats. J Urol, 1997, 157:2361~2365
7 Giuliani S, Lecci A, Tramontana M, et al. The inhibitory effect of nociceptin on the micturition reflex in anaesthetized rats. Br J Pharmacol, 1998, 124:1566~1572
8 Yoshimura N, Erdman SL, Snider MW, et al. Effects of spinal cord injury on neurofilament immunoreactivity and capsaicin sensitivity in rat dorsal root ganglion neurons innervating the urinary bladder. Neuroscience, 1998, 83:633~643
9 Zvara P, Sahi S, Hassouna MM. An animal model for theneuromodulation of neurogenic bladder dysfunction. Br J Urol, 1998, 82:267~271
10 Doi T, Kamo I, Imai S, et al. Effects of TAK-637, a tachykinin receptor antagonist, on lower urinary tract function in the guinea pig. Eur J Pharmacol, 1999, 383:297~303
11 Nickel RF, Venker-van AJ. Functional anatomy and neural regulation of the lower urinary tract in female dogs: a review. Vet Quart, 1999, 21:83~85
12 Palea S, Pietra C. Involvement of spinal NK1 and opioids receptors in modulating the inhibitory effect of capsaicin on micturition reflex in the acute spinalized guinea pig. J Urol, 1999, 161:998~1005
13 Pandita RK, Fujiwara M, Alm P. Cystometric evaluation of bladder function in nonanesthetized mice with and without bladder outlet obstruction. J Urol, 2000, 164:1385~1389
14 Bae JH, Moon DG, Lee JG. The effects of a selective noradrenaline reuptake inhibitor on the urethra: an in vitro and in vivo study. Br J Urol Int, 2001, 88:771~775
15 Calvert RC, Thompson CS, Khan MA. Alterations in cholinergic and purinergic signaling in a model of the obstructed bladder. J Urol, 2001, 166:1530~1533
16 Lecci A, Carini F, Tramontana M, et al. Urodynamic effects induced by intravesical capsaicin in rats and hamsters. Auton Neurosci Basic Clin, 2001, 91:37~46
17 Dwyer PL, Glenning PP. Anatomy and neurology of thelower urinary tract. Curr Opin Obstet Gynecol, 1990, 2:573~579
18 Birder LA, De-groat WC. Induction of c-fos expression in spinal neurons by nociceptive and nonnociceptive stimulation of LUT. Am J Physiol, 1993, 265:326~333
19 Fletcher TF. Applied anatomy and physiology of the feline lower urinary tract. Vet Clin N Am, 1996, 26:181~196
20 Neuhaus J, Dorschner W, Mondry J. Comparative anatomy of the male guinea-pig and human lower urinary tract: histomorphology and three-dimensional reconstruction. Anat Histol Embryol Vet Med C, 2001, 30:185~192
21 Neuhaus J, Stolzenburg JU, Dorschner W. The guinea pig as a model in urological research-an anatomical study. Aktuel Urol, 1999, 30:329~334
22 Dass N, Mcmurray G, Greenland JE, et al. Morphological aspects of the female pig bladder neck and urethra: quantitative analysis using computer assisted 3-dimensional reconstructions. J Urol, 2001, 165:1294~1299
23 Ganzer R, Kohler D, Neuhaus J, et al. Is the rhesus monkey (Macaca mulatta) comparable to humans? Histomorphology of the sphincteric musculature of the lower urinary tract including 3D-reconstruction. Anat Histol Embryol Vet Med C, 2004, 33: 355~361
24 Ganzer R, Neuhaus J, Dorschner W, et al. Muscle systems of the lower urinary tract of the male rhesus monkey (Macaca mulatta): histomorphology and 3-dimensionalreconstruction. J Urol, 2002, 168:1603~1607
25 Silva WA, Karram MM. Anatomy and physiology of the pelvic floor. Minerva Ginecol, 2004, 56:283~302
26 De-groat WC, Yoshimura N. Pharmacology of the lower urinary tract. Annu Rev Pharmacol Toxicol, 2001, 41:691~721
27 De-groat WC. Anatomy of the central neural pathways controlling the lower urinary tract. Eur Urol, 1998, 1:2~5
28 Blok BFM, Holstege G. The central control of micturition and continence: implications for urology. Br J Urol Int, 1999, 83:1~6
29 Blok BF. Central pathways controlling micturition and urinary continence. Urology, 2002, 59:13~17
30 Brindley GS, Craggs MD. Proceedings: the effect of atropine on the urinary bladder of the baboon and of man. J Physiol, 1976, 256: 55
31 Brading AF, Mostwin JL. Electrical and mechanical responses of guinea-pig bladder muscle to nerve stimulation. Br J Pharmacol, 1989, 98:1083~1090
32 Hashitani H, Bramich NJ, Hirst GD. Mechanisms of excitatory neuromuscular transmission in the guinea-pig urinary bladder. J Physiol, 2000, 524:565~579
33 Pessina F, Marazova K, Kalfin R, et al. Mechanical response to electrical field stimulation of rat, guinea-pig, monkey and human detrusor muscle: a comparative study. Naunyn-Schmiedebergs Arch Pharmacol, 2001,363:543~550
34 Bayliss M, Wu C, Newgreen D, et al. A quantitative study of atropine-resistant contractile responses in human detrusor smooth muscle, from stable, unstable and obstructed bladders. J Urol, 1999, 162:1833~1839
35 Elneil S, Skepper JN, Kidd EJ, et al. Distribution of P2X(1) and P2X(3) receptors in the rat and human urinary bladder. Pharmacology, 2001, 63:120~128
36 Palea S, Artibani W, Ostardo E, et al. Evidence for purinergic neurotransmission in human urinary bladder affected by interstitial cystitis. J Urol, 1993, 150:2007~2012
37 Gabella G, Uvelius B. Urinary bladder of rat: fine structure of normal and hypertrophic musculature. Cell Tissue Res, 1990, 262:67~69
38 Birder LA, Nakamura Y, Kiss S, et al. Altered urinary bladder function in mice lacking the vanilloid receptor TRPV1. Nat Neurosci, 2002, 5:856~860
39 Ishizuka O, Mattiasson A, Andersson KE. Urodynamic effects of intravesical resiniferatoxin and capsaicin in conscious rats with and without outflow obstruction. J Urol, 1995, 154:611~616
40 Modiri AR, Alberts P, Gillberg PG. Effect of muscarinic antagonists on micturition pressure measured by cystometry in normal, conscious rats. Urology, 2002, 59:963~968
41 Lecci A, Giuliani S, Garret C, et al. Evidence for a role of tachykinins as sensory transmitters in the activation ofmicturition reflex. Neuroscience, 1993, 54:827~837
42 Yoshiyama M, Roppolo JR, Thor KB, et al. Effects of LY274614, a competitive NMDA receptor antagonist, on the micturition reflex in the urethane-anaesthetized rat. Br J Pharmacol, 1993, 110:77~86
43 Cheng CL, Liu JC, Chang SY, et al. Effect of capsaicin on the micturition reflex in normal and chronic spinal cord-injured cats. Am J Physiol, 1999, 277: 786~794
44 Komiyama I, Igawa Y, Ishizuka O, et al. Effects of intravesical capsaicin and resiniferatoxin on distension-induced bladder contraction in conscious rats with and without chronic spinal cord injury. J Urol, 1999, 161:314~319
45 Lecci A, Giuliani S, Tramontana M, et al. Multiple sites of action in the inhibitory effect of nociceptin on the micturition reflex. J Urol, 2000, 163:638~645
46 Kakizaki H, Yoshiyama M, Koyanagi T, et al. Effects of WAY100635, a selective 5-HT1A-receptor antagonist on the micturition-reflex pathway in the rat. Am J Physiol, 2001, 280:1407~1413
47 Testa R, Guarneri L, Angelico P, et al. Effect of different 5-hydroxytryptamine receptor subtype antagonists on the micturition reflex in rats. Br J Urol Int, 2001, 87:256~264
48 Mitsui T, Kakizaki H, Matsuura S, et al. Chemical bladder irritation provokes c-fos expression in the midbrain periaqueductal gray matter of the rat. Brain Res, 2003,967:81~88
49 Avelino A, Cruz F, Coimbra A. Intravesical resiniferatoxin desensitizes rat bladder sensory fibres without causing intense noxious excitation. A c-fos study. Eur J Pharmacol, 1999, 378:17~22
50 Zhang XY, Igawa Y, Ishizuka O, et al. Effects of resiniferatoxin desensitization of capsaicin-sensitive afferents on detrusor over-activity induced by intravesical capsaicin, acetic acid or ATP in conscious rats. Naunyn-Schmiedebergs Arch Pharmacol, 2003, 367:473~479
51 Mitsui T, Kakizaki H, Matsuura S, et al. Afferent fibers of the hypogastric nerves are involved in the facilitating effects of chemical bladder irritation in rats. J Neurophysiol, 2001, 86:2276~2284
52 Balmaseda JR, Reynolds HT, Gordon C. The value of the ice water test in the management of the neurogenic bladder. Am J Phys Med Rehabil, 1988, 67:225~227
53 Geirsson G, Fall M, Lindstrom S. The ice-water test – a simple and valuable supplement to routine cystometry. Br J Urol, 1993, 71:681~685
54 Geirsson G, Fall M, Sullivan L. Clinical and urodynamic effects of intravesical capsaicin treatment in patients with chronic traumatic spinal detrusor hyperreflexia. J Urol, 1995, 154:1825~1829
55 Ishigooka M, Hashimoto T, Hayami S, et al. Ice water test inpatients with overactive bladder due to cerebrovascular accidents and bladder outlet obstruction. Urol Int, 1997, 58:84~87
56 Ismael SS, Epstein T, Bayle B, et al. Bladder cooling reflex in patients with multiple sclerosis. J Urol, 2000, 164:1280~1284
57 Geirsson G, Lindstrom S, Fall M, et al. Positive bladder cooling test in neurologically normal young children. J Urol, 1994, 151:446~448
58 Fall M, Lindstrom S, Mazieres L. A bladder-to-bladder cooling reflex in the cat. J Physiol, 1990, 427:281~300
59 Mazieres L, Jiang C, Lindstrom S. The C fibre reflex of the cat urinary bladder. J Physiol, 1998, 513:531~541
60 Jiang C, Mazieres L, Lindstrom S. Cold and menthol sensitive C afferents of cat urinary bladder. J Physiol, 2002, 543:211~220
61 Gardiner JC, Westbrook S. Characterisation of a cold-induced micturition reflexin the anaesthetised guinea-pig, Abstract Viewer/Itinerary Planner. Washington, DC: Society for Neuroscience, 2003, Online, Program No. 189.5
62 Cheng CL, Chai CY, De-groat WC. Detrusorsphincter dyssynergia induced by cold stimulation of the urinary bladder of rats. Am J Physiol, 1997, 272:1271~1282
63 Ishizuka O, Igawa Y, Nishizawa O, et al. Role of supraspinal tachykinins for micturition in conscious ratswith and without bladder outlet obstruction. Naunyn-Schmiedebergs Arch Pharmacol, 2000, 361:543~548
64 Das AK, Leggett RE, Whitbeck C, et al. Effect of Doxazosin on rat urinary bladder function after partial outlet obstruction. Neurourol Urodynam, 2002, 21:160~166
65 Sibley GN. An experimental model of detrusor instability in the obstructed pig. Br J Urol, 1985, 57:292~298
66 Mostwin JL, Karim OM, Brooks EL, et al. The guinea-pig as a model of gradual urethral obstruction. J Urol, 1991, 145:854~858
67 Fabiyi AC, Gopalakrishnan M, Lynch JJ, et al. In vivo evaluation of the potency and bladder-vascular selectivity of the ATP-sensitive potassium channel openers (–)-cromakalim, ZD6169 and WAY-133537 in rats. Br J Urol Int, 2003, 91:284~290
68 Steers WD, Kolbeck S, Creedon D, et al. Nerve growth factor in the urinary bladder of the adult regulates neuronal form and function. J Clin Invest, 1991, 88:1709~1715
69 Steers WD, Creedon D, Tuttle JB. Immunity to nerve growth factor prevents afferent plasticity following urinary bladder hypertrophy. J Urol, 1996, 155:379~385
70 Tang H, Cefalu J, Nunn P, et al. Hyperactive voiding in spontaneously hypertensive rat (SHR): A comparative study between conscious cystometry and natural voiding models, Abstract Viewer/Itinerary Planner Orlando, FL: Society forNeuroscience, 2002, Online, Program No.68.7
71 Tong Y, Hung Y, Lin S, et al. The norepinephrine tissue concentration and neuropeptide Y immunoreactivity in genitourinary organs of the spontaneously hypertensive rat. J Auton Nerv Syst, 1996, 56:215~218
72 Clemow DB, Steers WD, Tuttle JB. Stretchactivated signaling of nerve growth factor secretion in bladder and vascular smooth muscle cells from hypertensive and hyperactive rats. J Cell Physiol, 2000, 183:289~300
73 Lee KS, Dean-mckinney T, Tuttle JB, et al. Intrathecal antisense oligonucleotide against the tetrodotoxin-resistant sodium channel (Nav1.8) reduces bladder hyperactivity in the spontaneously hypertensive rat. J Urol, 2002, 167:38
74 De-groat WC, Kawatani M, Hisamitsu T, et al. Mechanisms underlying the recovery of urinary bladder function following spinal cord injury. J Auton Nerv Syst, 1990, 30 (Suppl.):S71~S77
75 Yoshimura N, De-groat WC. Plasticity of Na+ channels in afferent neurones innervating rat urinary bladder following spinal cord injury. J Physiol, 1997, 503:269~276
76 Marianne DE, Pierre-alain J, Jean-pierre D, et al. Capsaicin and neurogenic detrusor hyperreflexia: a double-blind placebo-controlled study in 20 patients with spinal cord lesions. Neurourol Urodynam, 1998, 17:513~523
77 Dalmose AL, Bjarkam CR, Sorensen JC, et al. Effects of high frequency deep brain stimulation on urine storage andvoiding function in conscious minipigs. Neurourol Urodynam, 2004, 23:265~272
78 Kamo I, Torimoto K, Chancellor MB, et al. Urethral closure mechanisms under sneeze-induced stress condition in rats: a new animal model for evaluation of stress urinary incontinence. Am J Physiol, 2003, 285:356~365
79 Yokoyama O, Yoshiyama M, Namiki M, et al. Role of the forebrain in bladder overactivity following cerebral infarction in the rat. Exp Neurol, 2000, 163:469~476
80 Yokoyama O, Yusup A, Miwa Y, et al. Effects of tolterodine on an overactive bladder depend on suppression of C-fiber bladder afferent activity in rats. J Urol, 2005, 174:2032~2036
81 Yucel S, Baskin LS. An anatomical description of the male and female urethral sphincter complex. J Urol, 2004, 171:1890~1897
82 Brading AF. The physiology of the mammalian urinary outflow tract. Exp Physiol, 1999, 84:215~221
83 Van-asselt E, Groen J, Van-mastrigt R. A comparative study of voiding in rat and guinea-pig: simultaneous measurement of flow rate and pressure. Am J Physiol, 1995, 269:98~103
84 Katofiasc MA, Nissen J, Audia JE, et al. Comparison of the effects of serotonin selective, norepinephrine selective, and dual serotonin and norepinephrine reuptake inhibitors on lower urinary tract function in cats. Life Sci, 2002, 71:1227~1236
85 Buckner SA, Milicic I, Daza AV, et al. ABT-866, a novel α1A-adrenoceptor agonist with antagonist properties at the α1B- and α1D-adrenoceptor subtypes. Eur J Pharmacol, 2002, 449:159~165
86 Gregory SP. Developments in the understanding of the pathophysiology of urethral sphincter mechanism in competence in the bitch. Br Vet J, 1994, 150:135~150
87 Ali-el-dein B, Ghoneim MA. Effects of selective autonomic and pudendal denervation on the urethral function and development of retention in female dogs. J Urol, 2001, 166:1549~1554
88 Brune ME, O’neill AB, Gauvin DM, et al. Comparison of α1-adrenoceptor agonists in canine urethral pressure profilometry and abdominal leak point pressure models. J Urol, 2001, 166:1555~1559
89 Chermansky CJ, Cannon TW, Torimoto K, et al. A model of intrinsic sphincteric deficiency in the rat: electrocauterization. Neurourol Urodynam, 2004, 23:166~171
90 Rawlings C, Barsanti JA, Mahaffey MB, et al. Evaluation of colposuspension for treatment of incontinence in spayed female dogs. J Am Vet Med Assoc, 2001, 219:770~775
91 Kaiho Y, Kamo I, Sweeney D, et al. Effects of norepinephrine uptake inhibitor, nisoxetine, on the sneeze induced urethral continence mechanism in rats. Neurourol Urodyn, 2005, 24:569~570
2 顾方六, 主编. 现代前列腺病学. 人民军医出版社, 2003, 164~167
3 Owens PK, Fell AF, Coleman MW, et al. Chiral recognition in liquid chromatography utilizing chargeable cyclodextrins for resolution of doxazosin enantiomers. Chirality, 1997, 9 (2):184~190
4 Niu CQ, Ren LM. Chiral separation of three new antagonists of alpha-1 adrenoceptors by capillary electrophoresis. Acta Pharm Sin (药学学报), 2000, 35(6):451~453
5 Niu CQ, Ren LM. Chiral separation and preparation of three new antagonists of α1 adrenoceptors by chiral mobile phase HPLC. Acta Pharm Sin (药学学报), 2002, 37(6):450~453
6 Ma SP, Ren LM, Zhao D, et al. Chiral selective effects of doxazosin enantiomers on blood pressure and urinary bladder pressure in anesthetized rats. Acta Pharmacol Sin,2006, 27(11):1423~1430
7 田河林, 任雷鸣, 何东伟. 多沙唑嗪对映体对大鼠血压和排尿功能的影响. 中国药理学通报, 2007, 23(2):240~246
8 田河林, 任雷鸣. 多沙唑嗪对映体不同给药途径对豚鼠膀胱排尿功能的影响. 中国药理学与毒理学杂志, 2007, 21(2):118~123
9 金锡御, 吴雄飞, 主编. 尿道外科学. 人民卫生出版社, 2004, 55~59
10 Yamaguchi T, Nagano M, Osada Y. Effects of different alpha-1 adrenoceptor blockers on proximal urethral function using in vivo isovolumetric pressure changes. J Smooth Muscle Res, 2005, 41(5):247~256
11 Hattori Y, Kanno M. Role of α1-adrenoceptor subtypes in production of the positive inotropic effects in mammalian myocardium implications for the α1-adrenoceptor subtype distribution. Life Sci, 1998, 62 (17-18):1449~1453
12 严干新, 汤树本, 张海燕. 苯肾上腺素对豚鼠和兔离体心室乳头肌的作用. 生理学报, 1986, 38(6):619~626
13 Satoh M, Enomoto K, Niwano H, et al. Regional differences in α 1-adrenoceptor subtypes in rabbit arteries. Eur J Pharmacol, 1998, 350(1):67~73
14 Satoh M, Enomoto K, Takayanagi I, et al. Analysis of α 1-adrenoceptor subtypes in rabbit aorta and arteries: regional difference and co-existence. Eur J Pharmacol, 1999, 374(2):229~240
15 孙则禹. 肾上腺素能受体与下尿路症状. 江苏医药, 2005, 31(3):214~215
1 Kirby RS, Andersen M, Gratzke P, et al. A combined analysis of double-blind trial of the efficacy and tolerability of doxazosin-gastrointestinal therapeutic system, doxazosin, standard and placebo in patients with BPH. BJU Int, 2001, 87(3):192~200
2 潘启超. 新α1受体阻断剂-多沙唑嗪的药理及临床(一). 广州医药, 1999, 30(5):6~7
3 卢竟前, 曹晶茗. 多沙唑嗪应用于心血管病的研究进展. 现代中西医结合杂志. 2005, 14(9):1242~1244
4 MacDonald R, Wilt TJ, Howe RW. Doxazosin for treating lower tract symptoms compatible with benign prostatic obstruction:a systematic review of efficacy and adverse effects. BJU Int, 2004, 94(9):1263~1270
5 Owens PK, Fell AF, Coleman MW, et al. Chiral recognition in liquid chromatography utilizing chargeable cyclodextrins for resolution of doxazosin enantiomers. Chirality, 1997, 9(2):184~190
6 Niu CQ, Ren LM. Chiral separation of three new antagonists of alpha-1 adrenoceptors by capillary electrophoresis. Acta Pharm Sin(药学学报), 2000, 35(6):451~453
7 Niu CQ, Ren LM. Chiral separation and preparation of threenew antagonists of α1 adrenoceptors by chiral mobile phase HPLC. Acta Pharm Sin(药学学报), 2002, 37(6):450~453
8 Ma SP, Ren LM, Zhao D, et al. Chiral selective effects of doxazosin enantiomers on blood pressure and urinary bladder pressure in anesthetized rats. Acta Pharmac Sin, 2006, 27(11):1423~1430
9 田河林, 任雷鸣, 何东伟. 多沙唑嗪对映体对大鼠血压和排尿功能的影响. 中国药理学通报, 2007, 23(2):240~246
10 田河林, 任雷鸣. 多沙唑嗪对映体不同给药途径对豚鼠膀胱排尿功能的影响. 中国药理学与毒理学杂志, 2007, 21(2):118~123
11 Yamaguchi T, Nagano M, Osada Y. Effects of different alpha-1 adrenoceptor blockers on proximal urethral function using in vivo isovolumetric pressure changes. J Smooth Muscle Res, 2005, 41(5):247~256
12 孙则禹. 肾上腺素能受体与下尿路症状. 江苏医药, 2005, 31(3):214~215
13 Sica DA. Doxazosin and congestive heart failure. Congest Heart Fail, 2002, 8(3):178~184
14 Hatano A, Tang R, Walden PD, et al. The α-adrenoceptor antagonist properties of the enantiomers of doxazosin in human prostate. Eur J Pharmacol, 1996, 313(1-2):135~143
15 卢海刚, 赵丁, 任雷鸣. 多沙唑嗪对映体对兔离体膀胱逼尿肌的作用和作用机制. 中国药理学通报, 2008, 24(4):513~517
16 Niu CQ, Zhao D, Jia XM, et al. α1-Adrenoceptor antagonist profile of doxazosin and its enantiomers in isolated rabbit blood vessels. Chin J Pharmacol Toxical (中国药理学与毒理学杂志), 2003, 17(5):354~359
17 卢海刚, 刘丽芳, 任雷鸣. 多沙唑嗪对映体对兔四种血管α受体的作用. 药学学报, 2007, 42(2):145~151
1 Harada T, Kumazaki T, Kigure T, et al. Effect of adrenergic agents on urethral pressure and urethral compliance measurements in dog proximal urethra. J Urol, 1989, 142:189~192
2 Kontani H, Nakagawa M, Sakai T. Effects of adrenergic agonists on an experimental urinary incontinence model in anesthetized rabbits. Jap J Pharmacol. 1992, 58:339~346
3 Yoshimura N, Mizuta E, Kuno S, et al. The dopamine D1 receptor agonist SKF 38393 suppresses detrusor hyperreflexia in the monkey with parkinsonism induced by 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP). Neuropharmacology, 1993, 32:315~321
4 Danuser H, Thor KB. Spinal 5-HT2 receptor-mediated facilitation of pudendal nerve reflexes in the anaesthetized cat. Br J Pharmacol, 1996, 118:150~154
5 Ghoniem GM, Shoukry MS, Monga M. Effects of anesthesia on urodynamic studies in the primate model. J Urol, 1996, 156:233~236
6 Watanabe T, Perkash I, Constantinou CE. Modulation of detrusor contraction strength and micturition characteristics by intrathecal baclofen in anesthetized rats. J Urol, 1997, 157:2361~2365
7 Giuliani S, Lecci A, Tramontana M, et al. The inhibitory effect of nociceptin on the micturition reflex in anaesthetized rats. Br J Pharmacol, 1998, 124:1566~1572
8 Yoshimura N, Erdman SL, Snider MW, et al. Effects of spinal cord injury on neurofilament immunoreactivity and capsaicin sensitivity in rat dorsal root ganglion neurons innervating the urinary bladder. Neuroscience, 1998, 83:633~643
9 Zvara P, Sahi S, Hassouna MM. An animal model for theneuromodulation of neurogenic bladder dysfunction. Br J Urol, 1998, 82:267~271
10 Doi T, Kamo I, Imai S, et al. Effects of TAK-637, a tachykinin receptor antagonist, on lower urinary tract function in the guinea pig. Eur J Pharmacol, 1999, 383:297~303
11 Nickel RF, Venker-van AJ. Functional anatomy and neural regulation of the lower urinary tract in female dogs: a review. Vet Quart, 1999, 21:83~85
12 Palea S, Pietra C. Involvement of spinal NK1 and opioids receptors in modulating the inhibitory effect of capsaicin on micturition reflex in the acute spinalized guinea pig. J Urol, 1999, 161:998~1005
13 Pandita RK, Fujiwara M, Alm P. Cystometric evaluation of bladder function in nonanesthetized mice with and without bladder outlet obstruction. J Urol, 2000, 164:1385~1389
14 Bae JH, Moon DG, Lee JG. The effects of a selective noradrenaline reuptake inhibitor on the urethra: an in vitro and in vivo study. Br J Urol Int, 2001, 88:771~775
15 Calvert RC, Thompson CS, Khan MA. Alterations in cholinergic and purinergic signaling in a model of the obstructed bladder. J Urol, 2001, 166:1530~1533
16 Lecci A, Carini F, Tramontana M, et al. Urodynamic effects induced by intravesical capsaicin in rats and hamsters. Auton Neurosci Basic Clin, 2001, 91:37~46
17 Dwyer PL, Glenning PP. Anatomy and neurology of thelower urinary tract. Curr Opin Obstet Gynecol, 1990, 2:573~579
18 Birder LA, De-groat WC. Induction of c-fos expression in spinal neurons by nociceptive and nonnociceptive stimulation of LUT. Am J Physiol, 1993, 265:326~333
19 Fletcher TF. Applied anatomy and physiology of the feline lower urinary tract. Vet Clin N Am, 1996, 26:181~196
20 Neuhaus J, Dorschner W, Mondry J. Comparative anatomy of the male guinea-pig and human lower urinary tract: histomorphology and three-dimensional reconstruction. Anat Histol Embryol Vet Med C, 2001, 30:185~192
21 Neuhaus J, Stolzenburg JU, Dorschner W. The guinea pig as a model in urological research-an anatomical study. Aktuel Urol, 1999, 30:329~334
22 Dass N, Mcmurray G, Greenland JE, et al. Morphological aspects of the female pig bladder neck and urethra: quantitative analysis using computer assisted 3-dimensional reconstructions. J Urol, 2001, 165:1294~1299
23 Ganzer R, Kohler D, Neuhaus J, et al. Is the rhesus monkey (Macaca mulatta) comparable to humans? Histomorphology of the sphincteric musculature of the lower urinary tract including 3D-reconstruction. Anat Histol Embryol Vet Med C, 2004, 33: 355~361
24 Ganzer R, Neuhaus J, Dorschner W, et al. Muscle systems of the lower urinary tract of the male rhesus monkey (Macaca mulatta): histomorphology and 3-dimensionalreconstruction. J Urol, 2002, 168:1603~1607
25 Silva WA, Karram MM. Anatomy and physiology of the pelvic floor. Minerva Ginecol, 2004, 56:283~302
26 De-groat WC, Yoshimura N. Pharmacology of the lower urinary tract. Annu Rev Pharmacol Toxicol, 2001, 41:691~721
27 De-groat WC. Anatomy of the central neural pathways controlling the lower urinary tract. Eur Urol, 1998, 1:2~5
28 Blok BFM, Holstege G. The central control of micturition and continence: implications for urology. Br J Urol Int, 1999, 83:1~6
29 Blok BF. Central pathways controlling micturition and urinary continence. Urology, 2002, 59:13~17
30 Brindley GS, Craggs MD. Proceedings: the effect of atropine on the urinary bladder of the baboon and of man. J Physiol, 1976, 256: 55
31 Brading AF, Mostwin JL. Electrical and mechanical responses of guinea-pig bladder muscle to nerve stimulation. Br J Pharmacol, 1989, 98:1083~1090
32 Hashitani H, Bramich NJ, Hirst GD. Mechanisms of excitatory neuromuscular transmission in the guinea-pig urinary bladder. J Physiol, 2000, 524:565~579
33 Pessina F, Marazova K, Kalfin R, et al. Mechanical response to electrical field stimulation of rat, guinea-pig, monkey and human detrusor muscle: a comparative study. Naunyn-Schmiedebergs Arch Pharmacol, 2001,363:543~550
34 Bayliss M, Wu C, Newgreen D, et al. A quantitative study of atropine-resistant contractile responses in human detrusor smooth muscle, from stable, unstable and obstructed bladders. J Urol, 1999, 162:1833~1839
35 Elneil S, Skepper JN, Kidd EJ, et al. Distribution of P2X(1) and P2X(3) receptors in the rat and human urinary bladder. Pharmacology, 2001, 63:120~128
36 Palea S, Artibani W, Ostardo E, et al. Evidence for purinergic neurotransmission in human urinary bladder affected by interstitial cystitis. J Urol, 1993, 150:2007~2012
37 Gabella G, Uvelius B. Urinary bladder of rat: fine structure of normal and hypertrophic musculature. Cell Tissue Res, 1990, 262:67~69
38 Birder LA, Nakamura Y, Kiss S, et al. Altered urinary bladder function in mice lacking the vanilloid receptor TRPV1. Nat Neurosci, 2002, 5:856~860
39 Ishizuka O, Mattiasson A, Andersson KE. Urodynamic effects of intravesical resiniferatoxin and capsaicin in conscious rats with and without outflow obstruction. J Urol, 1995, 154:611~616
40 Modiri AR, Alberts P, Gillberg PG. Effect of muscarinic antagonists on micturition pressure measured by cystometry in normal, conscious rats. Urology, 2002, 59:963~968
41 Lecci A, Giuliani S, Garret C, et al. Evidence for a role of tachykinins as sensory transmitters in the activation ofmicturition reflex. Neuroscience, 1993, 54:827~837
42 Yoshiyama M, Roppolo JR, Thor KB, et al. Effects of LY274614, a competitive NMDA receptor antagonist, on the micturition reflex in the urethane-anaesthetized rat. Br J Pharmacol, 1993, 110:77~86
43 Cheng CL, Liu JC, Chang SY, et al. Effect of capsaicin on the micturition reflex in normal and chronic spinal cord-injured cats. Am J Physiol, 1999, 277: 786~794
44 Komiyama I, Igawa Y, Ishizuka O, et al. Effects of intravesical capsaicin and resiniferatoxin on distension-induced bladder contraction in conscious rats with and without chronic spinal cord injury. J Urol, 1999, 161:314~319
45 Lecci A, Giuliani S, Tramontana M, et al. Multiple sites of action in the inhibitory effect of nociceptin on the micturition reflex. J Urol, 2000, 163:638~645
46 Kakizaki H, Yoshiyama M, Koyanagi T, et al. Effects of WAY100635, a selective 5-HT1A-receptor antagonist on the micturition-reflex pathway in the rat. Am J Physiol, 2001, 280:1407~1413
47 Testa R, Guarneri L, Angelico P, et al. Effect of different 5-hydroxytryptamine receptor subtype antagonists on the micturition reflex in rats. Br J Urol Int, 2001, 87:256~264
48 Mitsui T, Kakizaki H, Matsuura S, et al. Chemical bladder irritation provokes c-fos expression in the midbrain periaqueductal gray matter of the rat. Brain Res, 2003,967:81~88
49 Avelino A, Cruz F, Coimbra A. Intravesical resiniferatoxin desensitizes rat bladder sensory fibres without causing intense noxious excitation. A c-fos study. Eur J Pharmacol, 1999, 378:17~22
50 Zhang XY, Igawa Y, Ishizuka O, et al. Effects of resiniferatoxin desensitization of capsaicin-sensitive afferents on detrusor over-activity induced by intravesical capsaicin, acetic acid or ATP in conscious rats. Naunyn-Schmiedebergs Arch Pharmacol, 2003, 367:473~479
51 Mitsui T, Kakizaki H, Matsuura S, et al. Afferent fibers of the hypogastric nerves are involved in the facilitating effects of chemical bladder irritation in rats. J Neurophysiol, 2001, 86:2276~2284
52 Balmaseda JR, Reynolds HT, Gordon C. The value of the ice water test in the management of the neurogenic bladder. Am J Phys Med Rehabil, 1988, 67:225~227
53 Geirsson G, Fall M, Lindstrom S. The ice-water test – a simple and valuable supplement to routine cystometry. Br J Urol, 1993, 71:681~685
54 Geirsson G, Fall M, Sullivan L. Clinical and urodynamic effects of intravesical capsaicin treatment in patients with chronic traumatic spinal detrusor hyperreflexia. J Urol, 1995, 154:1825~1829
55 Ishigooka M, Hashimoto T, Hayami S, et al. Ice water test inpatients with overactive bladder due to cerebrovascular accidents and bladder outlet obstruction. Urol Int, 1997, 58:84~87
56 Ismael SS, Epstein T, Bayle B, et al. Bladder cooling reflex in patients with multiple sclerosis. J Urol, 2000, 164:1280~1284
57 Geirsson G, Lindstrom S, Fall M, et al. Positive bladder cooling test in neurologically normal young children. J Urol, 1994, 151:446~448
58 Fall M, Lindstrom S, Mazieres L. A bladder-to-bladder cooling reflex in the cat. J Physiol, 1990, 427:281~300
59 Mazieres L, Jiang C, Lindstrom S. The C fibre reflex of the cat urinary bladder. J Physiol, 1998, 513:531~541
60 Jiang C, Mazieres L, Lindstrom S. Cold and menthol sensitive C afferents of cat urinary bladder. J Physiol, 2002, 543:211~220
61 Gardiner JC, Westbrook S. Characterisation of a cold-induced micturition reflexin the anaesthetised guinea-pig, Abstract Viewer/Itinerary Planner. Washington, DC: Society for Neuroscience, 2003, Online, Program No. 189.5
62 Cheng CL, Chai CY, De-groat WC. Detrusorsphincter dyssynergia induced by cold stimulation of the urinary bladder of rats. Am J Physiol, 1997, 272:1271~1282
63 Ishizuka O, Igawa Y, Nishizawa O, et al. Role of supraspinal tachykinins for micturition in conscious ratswith and without bladder outlet obstruction. Naunyn-Schmiedebergs Arch Pharmacol, 2000, 361:543~548
64 Das AK, Leggett RE, Whitbeck C, et al. Effect of Doxazosin on rat urinary bladder function after partial outlet obstruction. Neurourol Urodynam, 2002, 21:160~166
65 Sibley GN. An experimental model of detrusor instability in the obstructed pig. Br J Urol, 1985, 57:292~298
66 Mostwin JL, Karim OM, Brooks EL, et al. The guinea-pig as a model of gradual urethral obstruction. J Urol, 1991, 145:854~858
67 Fabiyi AC, Gopalakrishnan M, Lynch JJ, et al. In vivo evaluation of the potency and bladder-vascular selectivity of the ATP-sensitive potassium channel openers (–)-cromakalim, ZD6169 and WAY-133537 in rats. Br J Urol Int, 2003, 91:284~290
68 Steers WD, Kolbeck S, Creedon D, et al. Nerve growth factor in the urinary bladder of the adult regulates neuronal form and function. J Clin Invest, 1991, 88:1709~1715
69 Steers WD, Creedon D, Tuttle JB. Immunity to nerve growth factor prevents afferent plasticity following urinary bladder hypertrophy. J Urol, 1996, 155:379~385
70 Tang H, Cefalu J, Nunn P, et al. Hyperactive voiding in spontaneously hypertensive rat (SHR): A comparative study between conscious cystometry and natural voiding models, Abstract Viewer/Itinerary Planner Orlando, FL: Society forNeuroscience, 2002, Online, Program No.68.7
71 Tong Y, Hung Y, Lin S, et al. The norepinephrine tissue concentration and neuropeptide Y immunoreactivity in genitourinary organs of the spontaneously hypertensive rat. J Auton Nerv Syst, 1996, 56:215~218
72 Clemow DB, Steers WD, Tuttle JB. Stretchactivated signaling of nerve growth factor secretion in bladder and vascular smooth muscle cells from hypertensive and hyperactive rats. J Cell Physiol, 2000, 183:289~300
73 Lee KS, Dean-mckinney T, Tuttle JB, et al. Intrathecal antisense oligonucleotide against the tetrodotoxin-resistant sodium channel (Nav1.8) reduces bladder hyperactivity in the spontaneously hypertensive rat. J Urol, 2002, 167:38
74 De-groat WC, Kawatani M, Hisamitsu T, et al. Mechanisms underlying the recovery of urinary bladder function following spinal cord injury. J Auton Nerv Syst, 1990, 30 (Suppl.):S71~S77
75 Yoshimura N, De-groat WC. Plasticity of Na+ channels in afferent neurones innervating rat urinary bladder following spinal cord injury. J Physiol, 1997, 503:269~276
76 Marianne DE, Pierre-alain J, Jean-pierre D, et al. Capsaicin and neurogenic detrusor hyperreflexia: a double-blind placebo-controlled study in 20 patients with spinal cord lesions. Neurourol Urodynam, 1998, 17:513~523
77 Dalmose AL, Bjarkam CR, Sorensen JC, et al. Effects of high frequency deep brain stimulation on urine storage andvoiding function in conscious minipigs. Neurourol Urodynam, 2004, 23:265~272
78 Kamo I, Torimoto K, Chancellor MB, et al. Urethral closure mechanisms under sneeze-induced stress condition in rats: a new animal model for evaluation of stress urinary incontinence. Am J Physiol, 2003, 285:356~365
79 Yokoyama O, Yoshiyama M, Namiki M, et al. Role of the forebrain in bladder overactivity following cerebral infarction in the rat. Exp Neurol, 2000, 163:469~476
80 Yokoyama O, Yusup A, Miwa Y, et al. Effects of tolterodine on an overactive bladder depend on suppression of C-fiber bladder afferent activity in rats. J Urol, 2005, 174:2032~2036
81 Yucel S, Baskin LS. An anatomical description of the male and female urethral sphincter complex. J Urol, 2004, 171:1890~1897
82 Brading AF. The physiology of the mammalian urinary outflow tract. Exp Physiol, 1999, 84:215~221
83 Van-asselt E, Groen J, Van-mastrigt R. A comparative study of voiding in rat and guinea-pig: simultaneous measurement of flow rate and pressure. Am J Physiol, 1995, 269:98~103
84 Katofiasc MA, Nissen J, Audia JE, et al. Comparison of the effects of serotonin selective, norepinephrine selective, and dual serotonin and norepinephrine reuptake inhibitors on lower urinary tract function in cats. Life Sci, 2002, 71:1227~1236
85 Buckner SA, Milicic I, Daza AV, et al. ABT-866, a novel α1A-adrenoceptor agonist with antagonist properties at the α1B- and α1D-adrenoceptor subtypes. Eur J Pharmacol, 2002, 449:159~165
86 Gregory SP. Developments in the understanding of the pathophysiology of urethral sphincter mechanism in competence in the bitch. Br Vet J, 1994, 150:135~150
87 Ali-el-dein B, Ghoneim MA. Effects of selective autonomic and pudendal denervation on the urethral function and development of retention in female dogs. J Urol, 2001, 166:1549~1554
88 Brune ME, O’neill AB, Gauvin DM, et al. Comparison of α1-adrenoceptor agonists in canine urethral pressure profilometry and abdominal leak point pressure models. J Urol, 2001, 166:1555~1559
89 Chermansky CJ, Cannon TW, Torimoto K, et al. A model of intrinsic sphincteric deficiency in the rat: electrocauterization. Neurourol Urodynam, 2004, 23:166~171
90 Rawlings C, Barsanti JA, Mahaffey MB, et al. Evaluation of colposuspension for treatment of incontinence in spayed female dogs. J Am Vet Med Assoc, 2001, 219:770~775
91 Kaiho Y, Kamo I, Sweeney D, et al. Effects of norepinephrine uptake inhibitor, nisoxetine, on the sneeze induced urethral continence mechanism in rats. Neurourol Urodyn, 2005, 24:569~570