Kurihara H, Yoshizumi M, Sugiyama T, Yamaoki K, Nagai R, Takaku F, Satoh H, Inui J, Yanagisawa M, Masaki T
Third Department of Internal Medicine, University of Tokyo, Japan.
J Cardiovasc Pharmacol. 1989;13 Suppl 5:S132-7; discussion S142. doi: 10.1097/00005344-198900135-00033.
We investigated the in vivo vasoconstrictor effects of endothelin-1 (ET-1) on canine coronary arteries and the regulation of ET-1 gene expression with special reference to the pathogenesis of coronary vasospasm. ET-1, administered into the coronary arteries of anesthetized dogs, produced a profound and long-lasting reduction in coronary blood flow with myocardial ischemia. Coronary angiography revealed delayed filling of the distal branches and, in some cases, total occlusion in the epicardial portions of coronary arteries. The coronary vasoconstriction induced by ET-1 subsided after intracoronary administration of nitroglycerin. Pretreatment with the Ca2+-channel antagonist, nitrendipine, suppressed ET-1-induced vasoconstriction. In cultured porcine aortic endothelial cells, ET-1 gene expression was induced by agents related to thrombus formation, such as thrombin and transforming growth factor beta (TGF beta). These findings suggest that ET-1, produced by vascular endothelial cells, may contribute to the regulation of coronary circulation and the pathogenesis of coronary vasospasm with respect to intimal injury and subsequent thrombus formation.
我们研究了内皮素 -1（ET -1）对犬冠状动脉的体内血管收缩作用以及ET -1基因表达的调控，特别参考了冠状动脉痉挛的发病机制。将ET -1注入麻醉犬的冠状动脉后，可导致冠状动脉血流显著且持久地减少，并伴有心肌缺血。冠状动脉造影显示远端分支充盈延迟，在某些情况下，冠状动脉心外膜部分完全闭塞。冠状动脉内给予硝酸甘油后，ET -1诱导的冠状动脉收缩消退。用钙通道拮抗剂尼群地平预处理可抑制ET -1诱导的血管收缩。在培养的猪主动脉内皮细胞中，与血栓形成相关的因子，如凝血酶和转化生长因子β（TGFβ），可诱导ET -1基因表达。这些发现表明，血管内皮细胞产生的ET -1可能在冠状动脉循环调节以及冠状动脉痉挛的发病机制中起作用，涉及内膜损伤和随后的血栓形成。
