Goldschmidt J E, Tallarida R J
Department of Pharmacology, Temple University School of Medicine, Philadelphia, Pennsylvania.
J Pharmacol Exp Ther. 1991 Jun;257(3):1136-45.
Captopril, an angiotensin-converting enzyme inhibitor, reportedly can scavenge superoxide anion (O2-), a property attributed to its sulfhydryl group. The present investigation, using rabbit aortic rings precontracted with either norepinephrine or clonidine, was designed to determine whether captopril possesses an endothelium-dependent component of vasodilation related to its ability to protect endothelium-derived relaxing factor (EDRF) from superoxide-mediated destruction. Also studied were enalaprilat, a nonsulfhydryl angiotensin-converting enzyme-inhibitor, superoxide dismutase, and the sulfhydryl compounds glutathione (GSH), N-2-mercaptopropionylglycine (MPG) and N-acetylcysteine (NAC). Captopril, but not enalaprilat, caused dose-dependent relaxations in preconstricted aortic rings containing an intact endothelium. Rings denuded of endothelium were unresponsive to any dose of captopril. Captopril's vasodilation was not related to prostaglandin influence but was associated with an increase in cyclic GMP. Superoxide dismutase, GSH, MPG and NAC also produced endothelium-dependent relaxations similar to captopril. It was also demonstrated that endothelium-dependent relaxations to acetylcholine were enhanced by captopril, GSH, MPG and NAC but not by enalaprilat. In another set of experiments, the ability of captopril to inhibit superoxide-mediated inactivation of EDRF was examined. Pyrogallol, a potent generator of O2-, and superoxide dismutase, a scavenger of O2-, were used as a basis for comparing a possible scavenging effect of captopril. In preconstricted rings, pyrogallol elicited endothelium-dependent contractions that were attenuated by both captopril and superoxide dismutase. Similar effects were found with GSH, MPG and NAC but not with enalaprilat. These results suggest that captopril's endothelium-dependent vasodilation is due to its sulfhydryl group and the ability of the latter to scavenge O2-, thereby protecting EDRF.
据报道，卡托普利作为一种血管紧张素转换酶抑制剂，能够清除超氧阴离子（O2-），这一特性归因于其巯基。本研究使用预先用去甲肾上腺素或可乐定预收缩的兔主动脉环，旨在确定卡托普利是否具有与保护内皮衍生舒张因子（EDRF）免受超氧介导破坏能力相关的内皮依赖性舒张成分。同时还研究了依那普利拉（一种非巯基血管紧张素转换酶抑制剂）、超氧化物歧化酶以及巯基化合物谷胱甘肽（GSH）、N-2-巯基丙酰甘氨酸（MPG）和N-乙酰半胱氨酸（NAC）。卡托普利而非依那普利拉，在含有完整内皮的预收缩主动脉环中引起剂量依赖性舒张。去内皮的环对任何剂量的卡托普利均无反应。卡托普利的血管舒张作用与前列腺素影响无关，但与环磷酸鸟苷的增加有关。超氧化物歧化酶、GSH、MPG和NAC也产生类似于卡托普利的内皮依赖性舒张。还证明卡托普利、GSH、MPG和NAC可增强对乙酰胆碱的内皮依赖性舒张，但依那普利拉则无此作用。在另一组实验中，研究了卡托普利抑制超氧介导的EDRF失活的能力。焦性没食子酸（一种强效的O2-生成剂）和超氧化物歧化酶（一种O2-清除剂）被用作比较卡托普利可能的清除作用的基础。在预收缩环中，焦性没食子酸引起内皮依赖性收缩，卡托普利和超氧化物歧化酶均可使其减弱。GSH、MPG和NAC也有类似作用，但依那普利拉则无。这些结果表明，卡托普利的内皮依赖性血管舒张是由于其巯基以及后者清除O2-从而保护EDRF的能力。
