Wang Miao, Ren Xue-Jiao, Zhao Qing-Hua, Lin Li-Xin, Wang Xue, Zhao Yan, Ren Lei-Ming
a Institute of Chinese Integrative Medicine, Hebei Medical University, 361 East Zhong-shan Road, Shijiazhuang 050017, Hebei, P. R. China.
Can J Physiol Pharmacol. 2011 Dec;89(12):883-90. doi: 10.1139/y11-087. Epub 2011 Nov 24.
(-)Doxazosin, one of (±)doxazosin enantiomers, was speculated to have a pharmacological enantioselectivity between the cardiovascular system and the urinary system by comparison with (+)doxazosin. Therefore, to evaluate the potential benefits of (-)doxazosin in the treatment of benign prostate hyperplasia, we compared the effects of the 3 agents, using rat mesenteric artery preparations and obstructed bladder strips. Concentration-response curves for carbachol (contractile response) and isoprenaline (relaxant response) in detrusor muscle strips of the bladder outlet obstruction (BOO) rats were shifted to the left, with significant increases in the Emax values, and significant decreases in the EC50 values by comparison with the sham-operated rats (P < 0.05, n = 10). The enhanced responses in detrusor muscle strips of the BOO rats treated with (±)doxazosin and its enantiomers at 3 mg·(kg body mass)(-1)·day(-1) for 2 weeks returned to normal levels, and the 3 agents inhibited the enhanced responses to carbachol and isoprenaline to the same extent. On the other hand, the 3 agents uncompetitively inhibited the vasoconstrictive response curves for NA in the rat isolated mesenteric artery, and the pKB value of (-)doxazosin at vascular α1-adrenoceptors was significantly smaller (P < 0.05, n = 6) than that of (+)doxazosin or (±)doxazosin. In conclusion, although (-)doxazosin inhibits vascular functional α1-adrenoceptors more weakly than (+)doxazosin, both agents equally ameliorate the enhanced responses in detrusor muscle of BOO rats, suggesting that the chiral carbon atom in the molecular structure of doxazosin does not affect its beneficial effects in the bladder smooth muscle of BOO rats.
（-）多沙唑嗪是（±）多沙唑嗪对映体之一，通过与（+）多沙唑嗪比较，推测其在心血管系统和泌尿系统之间具有药理对映体选择性。因此，为了评估（-）多沙唑嗪在治疗良性前列腺增生方面的潜在益处，我们使用大鼠肠系膜动脉制剂和梗阻膀胱条带比较了这三种药物的作用。与假手术大鼠相比，膀胱出口梗阻（BOO）大鼠膀胱逼尿肌条带中卡巴胆碱（收缩反应）和异丙肾上腺素（舒张反应）的浓度-反应曲线向左移动，Emax值显著增加，EC50值显著降低（P<0.05，n = 10）。用（±）多沙唑嗪及其对映体以3mg·（kg体重）（-1）·天（-1）处理2周的BOO大鼠逼尿肌条带中增强的反应恢复到正常水平，并且这三种药物对卡巴胆碱和异丙肾上腺素增强反应的抑制程度相同。另一方面，这三种药物对大鼠离体肠系膜动脉中去甲肾上腺素的血管收缩反应曲线具有非竞争性抑制作用，并且（-）多沙唑嗪在血管α1-肾上腺素受体处的pKB值显著小于（+）多沙唑嗪或（±）多沙唑嗪（P<0.05，n = 6）。总之，尽管（-）多沙唑嗪对血管功能性α1-肾上腺素受体的抑制作用比（+）多沙唑嗪弱，但两种药物均能同等程度地改善BOO大鼠逼尿肌中的增强反应，这表明多沙唑嗪分子结构中的手性碳原子不影响其在BOO大鼠膀胱平滑肌中的有益作用。
