多沙唑嗪对映体对兔离体膀胱逼尿肌的作用及机制

目的观察多沙唑嗪(rac-DOX)及其对映体(S-DOX、R-DOX)对兔离体膀胱逼尿肌的作用并分析其机制。方法制备兔背侧和腹侧膀胱逼尿肌标本,记录药物或神经刺激诱发的膀胱平滑肌收缩反应。结果在兔背侧和腹侧膀胱逼尿肌标本,卡巴胆碱产生浓度依赖性收缩反应,两种标本的收缩反应差异无显著性(P>0·05)。在背侧膀胱逼尿肌标本,苯肾上腺素产生浓度依赖性收缩反应;但是,苯肾上腺素对腹侧膀胱逼尿肌无作用。S-DOX、R-DOX和rac-DOX在1μmol·L-1时,均可竞争性拮抗苯肾上腺素诱发的兔背侧膀胱逼尿肌收缩反应,其pKB值分别为7·44±0·19、7·39±0·14和7·38±0·30,三者的pKB值相同。电场刺激诱发兔背侧和腹侧膀胱逼尿肌产生稳定的收缩反应,该收缩反应被0·3μmol·L-1浓度的河豚毒素完全阻断。S-DOX、R-DOX和rac-DOX均抑制电场刺激诱发的背侧膀胱逼尿肌收缩反应(P<0·01),且三者的抑制作用强度差异无显著性(P>0·05);但是,它们对电场刺激诱发的腹侧膀胱逼尿肌收缩反应无影响。结论在兔离体膀胱背侧逼尿肌,S-DOX拮抗苯肾上腺素诱发收缩反应的pKB值与rac-DOX和R-DOX相同,三者尚能抑制电场刺激诱发的神经源性收缩反应。

Effects of doxazosin enantiomers on the rabbit isolated detrusor strips

Aim To study the effects of rac-doxazosin, S-doxazosin and R-doxazosin on contractile responses of the rabbit isolated detrusor strips. Methods Isometric contractile responses to drugs or electric field stimulation in the rabbit isolated dorsal and ventral detrusor strips were recorded. Results Carbachol produced contractile responses concentration-dependently in the dorsal and ventral detrusor strips, and the response curves for carbachol in the two kind of preparations were not significantly different(P>0.05). Phenylephrine induced contractile responses in a concentration-dependent manner in the dorsal detrusor strips, but not in the ventral detrusor strips. S-doxazosin, R-doxazosin and rac-doxazosin at 1 μmol·L-1 antagonized the phenylephrine-induced contractile responses competitively in the dorsal detrusor strips, and their pKB values were 7.44±0.19, 7.39±0.14 and 7.38±0.30, respectively. Three pKB values of doxazosin and its enantiomers were not significantly different from each other. Electric field stimulation produced a steady contractile response that was completely inhibited by tetrodotoxin at 0.3 μmol·L-1. S-doxazosin, R-doxazosin and rac-doxazosin significantly inhibited the contractile responses to electric field stimulation in the dorsal detrusor strips of the rabbit urinary bladder(P<0.05), and their inhibitory effects were not significantly different from each other(P>0.05). However, S-doxazosin, R-doxazosin and rac-doxazosin did not affect the responses to electric field stimulation in the ventral detrusor strips. Conclusion The pKB value of S-doxazosin against phenylephrine-induced contraction via-adrenoceptors is same to R-doxazosin and rac-doxazosin, and the three agents are able to inhibit the adrenergic contraction induced by electric field stimulation in dorsal detrusor strips of the rabbit urinary bladder.