Selective blockade by nicergoline of vascular responses elicited by stimulation of alpha1A-adrenoceptor subtype in the rat
Selective blockade by nicergoline of vascular responses elicited by stimulation of alpha1A-adrenoceptor subtype in the rat
复制标题
DOI：
10.1111/j.1472-8206.1999.tb00320.x
复制
发表时间：
1999-01-01
影响因子：
2.9
通讯作者：
Garay, RP
中科院分区：
文献类型：
--
作者：
Alvarez-Guerra, M;Bertholom, N;Garay, RP
尼麦角林对大鼠的α(1)-肾上腺素能阻断活性进行了重新检测，特别强调了α(1)-肾上腺素能受体亚型。在去髓大鼠中，尼麦角林和哌唑嗪单次小剂量(0.5ug/kg/min静脉注射)。对特定的α(1)-激动剂Crazoline(ED50=4.0+/-0.1、4.0+/-0.1和0.9+/-0.01微克/公斤静脉注射)，对照剂量-压力反应曲线的右移显著且相同。尼麦角林、哌唑嗪和赋形剂)。在离体肠系膜血管灌流床上，尼麦角林可强烈抑制Crazoline引起的升压反应，其抑制效应(Pa(2)=11.1+/-0.3)约为哌唑嗪(Pa(2)=9.5+/-0.3)的40倍。尼麦角林对去内皮血管的收缩作用比哌唑嗪弱20倍(尼麦角林和哌唑嗪的pA(2)分别为8.6+/-0.2和9.9+/-0.2)。氯乙基可乐定预处理对尼麦角林拮抗作用无明显影响(pA(2)=10.6+/-0.2)。用氯乙基可乐定(pK(I)=9.9+/-0.2)处理大鼠前脑膜后，尼麦角林与[H-3]-哌唑嗪结合的浓度比大鼠肝细胞膜低60倍(pK(I)=8.1+/-0.2)。最后，在所研究的尼麦角林代谢物中，鲁米利舍戈作为一种适度的α-拮抗剂(溴烟酸缺乏α(1)拮抗剂活性)。综上所述，尼麦角林是一种有效的、选择性的α(1A)-肾上腺素能受体亚型拮抗剂，是一种主要存在于阻力动脉的α(1)-受体亚型。(C)爱思唯尔，巴黎。
The alpha(1)-adrenergic blocking activity of nicergoline was re-examined in rats, with a particular emphasis on alpha(1)-adrenoceptor subtypes. In pithed rats, nicergoline and prazosin infused at a single small dose (0.5 mu g/kg/min i.v.) produced a substantial and identical shift to the right of the control dose presser response curve to the specific alpha(1)-agonist cirazoline (ED50 = 4.0 +/- 0.1, 4.0 +/- 0.1 and 0.9 +/- 0.01 mu g/kg i.v. for nicergoline, prazosin and vehicle respectively). In the isolated perfused mesenteric vascular bed, nicergoline strongly inhibited the presser responses elicited by cirazoline, with approximately 40-fold higher potency (pA(2) = 11.1 +/- 0.3) than prazosin (pA(2) = 9.5 +/- 0.3). Conversely, nicergoline was 20-fold less potent than prazosin to antagonize the contractile effects of cirazoline in isolated endothelium-denuded aorta (pA(2) = 8.6 +/- 0.2 and 9.9 +/- 0.2 for nicergoline and prazosin respectively). Pretreatment of mesenteric vascular beds with chloroethylclonidine did not significantly modify nicergoline antagonistic potency (pA(2) = 10.6 +/- 0.2). Nicergoline displaced [H-3]-prazosin bound to rat forebrain membranes pretreated with chloroethylclonidine (pK(i) = 9.9 +/- 0.2) at concentrations 60-fold lower than in rat liver membranes (pK(i) = 8.1 +/- 0.2). Finally, of the nicergoline metabolites studied, lumilysergol acted as a modest alpha, antagonist (bromonicotinic acid was devoid of alpha(1) antagonist activity). In conclusion, nicergoline is a potent and selective alpha(1A)-adrenoceptor subtype antagonist, an alpha(1)-adrenoceptor subtype which is mainly represented in resistance arteries. (C) Elsevier, Paris.