Pierre L N, Davenport A P
Clinical Pharmacology Unit, University of Cambridge, Addenbrooke's Hospital, England.
J Cardiovasc Pharmacol. 1998;31 Suppl 1:S74-6. doi: 10.1097/00005344-199800001-00024.
Endothelin (ET) has been implicated in cardiovascular disorders such as stroke and myocardial ischemia. Given the important role of the resistance vasculature in the control of blood flow, we investigated the ET receptors that mediate vasoconstriction in human small pial and coronary arteries supplying the brain and heart, respectively. ETA receptors were localized by autoradiography to the vascular smooth-muscle layer of pial, intracerebral, and intramyocardial arteries. In contrast, little ETB binding was observed. ET-1 was a more potent constrictor than ET-3 in both pial and coronary arteries. Biphasic ET-3 responses were obtained in four of 15 coronary arteries tested. The ETB agonist sarafotoxin S6c had little or no effect in these vessels. The nonpeptide, selective ETA receptor antagonist PD156707 caused a parallel shift to the right of the concentration-response curve to ET-1, yielding pA2 values of 9.17 +/- 0.07 and 8.38 +/- 0.17 in pial and coronary arteries, respectively. Slopes from Schild analysis were not significantly different from unity. These data suggest that ETA receptors predominate on the smooth-muscle layer of human small pial arteries. Coronary arteries also express mainly ETA receptors. However, a small population of contractile ETB receptors may also be present in some patients.
内皮素（ET）与中风和心肌缺血等心血管疾病有关。鉴于阻力血管系统在控制血流方面的重要作用，我们分别研究了介导人脑软膜小动脉和供应心脏的冠状动脉血管收缩的ET受体。通过放射自显影法将ETA受体定位到软膜、脑内和心肌内动脉的血管平滑肌层。相比之下，观察到的ETB结合很少。在软膜动脉和冠状动脉中，ET-1比ET-3是更强效的收缩剂。在15条测试的冠状动脉中有4条获得了双相ET-3反应。ETB激动剂沙拉毒素S6c在这些血管中几乎没有影响或没有影响。非肽类选择性ETA受体拮抗剂PD156707使ET-1浓度-反应曲线平行右移，在软膜动脉和冠状动脉中的pA2值分别为9.17±0.07和8.38±0.17。Schild分析的斜率与1无显著差异。这些数据表明，ETA受体在人脑软膜小动脉的平滑肌层中占主导地位。冠状动脉也主要表达ETA受体。然而，在一些患者中也可能存在少量收缩性ETB受体。
