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沙丁胺醇对犬冠状动脉血管舒张活性的研究。亚甲蓝的意外作用。

Study of the vasodilating activity of salbutamol on dog coronary arteries. Unexpected effects of methylene blue.

作者信息

Bernard F, Jouquey S, Hamon G

机构信息

Centre de Recherche Roussel-Uclaf, Romainville, France.

出版信息

Pharmacology. 1991;42(5):246-51. doi: 10.1159/000138804.

DOI:10.1159/000138804
PMID:1678890
Abstract

The vascular relaxant effect of salbutamol and its dependence on the endothelium were studied in the isolated dog coronary artery, precontracted with prostaglandin F2 alpha. Salbutamol induced a concentration-dependent relaxation which was partially inhibited by removal of endothelial cells. Atenolol 10(-6) mol/l, a beta 1-selective antagonist, inhibited the relaxant effect of salbutamol both in the presence and in the absence of endothelium. Conversely, ICI 118,551 10(-6) mol/l, a beta 2-selective antagonist, antagonized the response to salbutamol only in intact vessels. Methylene blue amplified markedly the relaxation to salbutamol but only in denuded rings. Therefore, the vasodilating effect of salbutamol on large coronary arteries seems to result from the stimulation of both, beta 1-receptors on smooth muscle cells and beta 2-receptors on endothelial cells, demonstrating the existence of the two types of adrenoceptors in the wall of large dog coronary arteries. In addition, the effect obtained with methylene blue in this study shed some doubts on its specificity as a guanylate cyclase inhibitor.

摘要

在前列腺素F2α预收缩的离体犬冠状动脉中,研究了沙丁胺醇的血管舒张作用及其对内皮的依赖性。沙丁胺醇诱导浓度依赖性舒张,去除内皮细胞后该舒张作用部分受到抑制。10(-6)mol/L的阿替洛尔(一种β1选择性拮抗剂)在有内皮和无内皮的情况下均抑制沙丁胺醇的舒张作用。相反,10(-6)mol/L的ICI 118,551(一种β2选择性拮抗剂)仅在完整血管中拮抗对沙丁胺醇的反应。亚甲蓝显著增强对沙丁胺醇的舒张作用,但仅在去内皮环中如此。因此,沙丁胺醇对大冠状动脉的血管舒张作用似乎源于对平滑肌细胞上β1受体和内皮细胞上β2受体的双重刺激,表明在大犬冠状动脉壁中存在两种类型的肾上腺素能受体。此外,本研究中用亚甲蓝获得的结果对其作为鸟苷酸环化酶抑制剂的特异性产生了一些疑问。

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