Piascik M T, Smith M S, Barron K W, Soltis E E
University of Kentucky, Department of Pharmacology, College of Medicine, Lexington.
J Pharmacol Exp Ther. 1993 Dec;267(3):1250-5.
The role of alpha-1 adrenoceptors sensitive and resistant to chloroethylclonidine (CEC) in the regulation of peripheral hemodynamics in the conscious rat has been examined. CEC treatment (15, 25 or 30 mg/kg i.p.) resulted in a sustained decrease in systemic arterial blood pressure and heart rate. These same concentrations reduced, but did not eliminate, [3H]prazosin binding sites in vascular smooth muscle homogenates. The effect of CEC administration on blood flow and regional vascular resistance was assessed using pulsed-Doppler flow probes implanted around the superior mesenteric and iliac arteries. CEC treatment resulted in a significant decrease in mesenteric and hindlimb resistance. Prazosin (3 or 5 mg/kg) reduced systemic arterial blood pressure and vascular resistance to a greater degree than did CEC. The dose-response curve for phenylephrine-induced increases in mesenteric or hindlimb vascular resistance was shifted only 2- to 10-fold to the right by CEC. Prazosin, by contrast, shifted the phenylephrine dose-response curve over 100-fold to the right. These data indicate that multiple alpha-1 adrenoceptor subtypes, both CEC sensitive and insensitive, participate in the regulation of blood flow to the gut and the hindlimb. Finally, CEC sensitive sites do not appear to play as prominent a role as insensitive sites in mediating the pressor response to phenylephrine.
已研究了对氯乙可乐定（CEC）敏感和耐药的α-1肾上腺素能受体在清醒大鼠外周血流动力学调节中的作用。CEC处理（腹腔注射15、25或30mg/kg）导致全身动脉血压和心率持续下降。这些相同浓度降低了血管平滑肌匀浆中[3H]哌唑嗪结合位点，但并未消除。使用植入肠系膜上动脉和髂动脉周围的脉冲多普勒血流探头评估CEC给药对血流和局部血管阻力的影响。CEC处理导致肠系膜和后肢阻力显著降低。哌唑嗪（3或5mg/kg）比CEC更能降低全身动脉血压和血管阻力。去氧肾上腺素诱导的肠系膜或后肢血管阻力增加的剂量反应曲线仅因CEC向右移动2至10倍。相比之下，哌唑嗪使去氧肾上腺素剂量反应曲线向右移动超过100倍。这些数据表明，多种α-1肾上腺素能受体亚型，包括对CEC敏感和不敏感的亚型，都参与了肠道和后肢血流的调节。最后，在介导对去氧肾上腺素的升压反应中，对CEC敏感的位点似乎不如不敏感的位点起突出作用。
