Minato H, Hashizume M, Masuda Y, Hosoki K
Department of Pharmacology, Dainippon Pharmaceutical Co. Ltd., Osaka, Japan.
Arzneimittelforschung. 1995 Jun;45(6):675-8.
The present study was undertaken to investigate the role of endothelium in extraluminally induced vasospasm of the cerebral artery using isolated perfused canine basilar arteries. The extraluminal applications of high K+ and prostaglandin F2 alpha (PGF2 alpha) induced concentration-dependent vasoconstriction. Both constrictive responses were significantly enhanced by denuding endothelium. Additionally, the responses in the endothelium-intact arteries were markedly augmented by intraluminal perfusion with NG-monomethyl-L-arginine (L-NMMA). These results suggest that the inhibition of nitric oxide (NO) synthase in endothelium enhances increase in transmembrane Ca(2+)-influx which is a common constrictive mechanism to the vasoconstrictors. The augmentative action induced by L-NMMA was inhibited by intraluminal perfusion of L-arginine, but not by D-arginine. Furthermore, the augmentation was not observed in the arteries without endothelium. These results suggest that the endothelium may have a great significance on responsiveness to extraluminal vasoactive substances and that endothelium-derived NO may modulate the extraluminally induced vasoconstriction which is responsible for cerebral vasospasm after subarachnoid hemorrhage.
本研究旨在利用离体灌注犬基底动脉，探讨内皮在脑动脉腔外诱导血管痉挛中的作用。腔外应用高钾和前列腺素F2α（PGF2α）可诱导浓度依赖性血管收缩。去除内皮后，两种收缩反应均显著增强。此外，内皮完整的动脉腔内灌注N-甲基-L-精氨酸（L-NMMA）后，反应明显增强。这些结果表明，内皮中一氧化氮（NO）合酶的抑制会增强跨膜Ca（2+）内流的增加，这是血管收缩剂共同的收缩机制。L-NMMA诱导的增强作用可被腔内灌注L-精氨酸抑制，但不能被D-精氨酸抑制。此外，在无内皮的动脉中未观察到增强作用。这些结果表明，内皮可能对腔外血管活性物质的反应性具有重要意义，并且内皮衍生的NO可能调节腔外诱导的血管收缩，而这种收缩与蛛网膜下腔出血后的脑血管痉挛有关。
