Tabrizchi R, Triggle C R
Department of Pharmacology and Therapeutics, Faculty of Medicine, University of Calgary, Alberta, Canada.
J Cardiovasc Pharmacol. 1992 Apr;19(4):562-7. doi: 10.1097/00005344-199204000-00013.
The interrelationship between the effects of the angiotensin converting enzyme inhibitor captopril and the calcium channel antagonist nifedipine on alpha-mediated vasoconstriction elicited by the administration of the full and partial alpha 1-adrenoceptor agonists St 587 and cirazoline, respectively, and the alpha 2-adrenoceptor agonist B-HT 920 were examined in pithed normotensive rats. Treatment with captopril was found to attenuate pressor responses produced by the administration of either alpha 1- or alpha 2-adrenoceptor agonists, resulting in the displacement to the right of the agonist dose-response curves and significantly increasing the calculated ED50 values. The maximum response was unaltered and the calculated dose ratios for alpha-agonists in the presence or absence of captopril were found to be 3, 4.6, and 3.8 for B-HT 920, St 587, and cirazoline, respectively. In comparison, nifedipine displaced the dose-response curves for all three alpha-agonists to the right but only significantly increased the ED50 values for the partial alpha 1-agonist St 587 and the alpha 2-agonist B-HT 920, with the calculated dose ratios being 3.2 and 3.8, respectively. Following treatment with nifedipine, however, the maximum responses were significantly reduced. A combination of captopril and nifedipine did not result in any significant additive increase in the ED50 values compared to those obtained with captopril or nifedipine alone. However, the inhibition of the maximum response to B-HT 920 by a combination of captopril and nifedipine was additive.(ABSTRACT TRUNCATED AT 250 WORDS)
在脊髓横断的正常血压大鼠中,研究了血管紧张素转换酶抑制剂卡托普利和钙通道拮抗剂硝苯地平分别对由完全和部分α1-肾上腺素能受体激动剂St 587和可乐定以及α2-肾上腺素能受体激动剂B-HT 920引起的α介导的血管收缩作用之间的相互关系。发现用卡托普利治疗可减弱由α1-或α2-肾上腺素能受体激动剂给药产生的升压反应,导致激动剂剂量-反应曲线右移,并显著增加计算出的ED50值。最大反应未改变,并且发现存在或不存在卡托普利时α激动剂的计算剂量比对于B-HT 920、St 587和可乐定分别为3、4.6和3.8。相比之下,硝苯地平使所有三种α激动剂的剂量-反应曲线右移,但仅显著增加部分α1-激动剂St 587和α2-激动剂B-HT 920的ED50值,计算出的剂量比分别为3.2和3.8。然而,用硝苯地平治疗后,最大反应显著降低。与单独使用卡托普利或硝苯地平相比,卡托普利和硝苯地平联合使用并未导致ED50值有任何显著的累加增加。然而,卡托普利和硝苯地平联合使用对B-HT 920最大反应的抑制作用是累加的。(摘要截短于250字)