Climent Belén, Fernández Nuria, García-Villalón Angel Luis, Monge Luis, Sánchez Ana, Diéguez Godofredo
Departamento de Fisiología, Facultad de Medicina, Universidad Autónoma, Arzobispo Morcillo, 2, 28029 Madrid, Spain.
Vascul Pharmacol. 2006 May;44(5):384-90. doi: 10.1016/j.vph.2006.02.003. Epub 2006 Mar 3.
To compare the effects of antagonists for endothelin ET(A) and ET(B) receptors on the action of ischemia-reperfusion on endothelial and myocardial function, 30 min of partial or total occlusion followed by 60 min of reperfusion of the left circumflex coronary artery was induced in anesthetized goats treated with intracoronary administration of saline (vehicle), BQ-123 (endothelin ET(A) receptors antagonist) or BQ-788 (endothelin ET(B) receptors antagonist). During reperfusion after partial occlusion, coronary vascular conductance and left ventricle dP/dt were decreased after saline or BQ-788, and they normalized after BQ-123. In these three groups of animals, the coronary effects of acetylcholine (3-100 ng) and sodium nitroprusside (1-10 microg) during reperfusion were as under control. During reperfusion after total occlusion, coronary vascular conductance and left ventricle dP/dt were decreased after saline, and they normalized after BQ-123 or BQ-788. In these three groups of animals, the coronary effects of acetylcholine but not those of sodium nitroprusside during reperfusion were decreased after saline, and they reversed after BQ-123 or BQ-788. Therefore, selective antagonists of endothelin ET(B) and ET(A) receptors may produce similar protection of coronary vasculature and myocardium against reperfusion after severe ischemia. Selective antagonists of endothelin ET(B) receptors, contrarily to those of endothelin ET(A) receptors, may be ineffective to protect coronary vasculature and myocardium against reperfusion after mild ischemia.
为比较内皮素ET(A)和ET(B)受体拮抗剂对缺血再灌注作用于内皮和心肌功能的影响，对经冠状动脉内注射生理盐水（溶媒）、BQ-123（内皮素ET(A)受体拮抗剂）或BQ-788（内皮素ET(B)受体拮抗剂）处理的麻醉山羊，诱导其左回旋支冠状动脉部分或完全闭塞30分钟，随后再灌注60分钟。在部分闭塞后的再灌注期间，生理盐水或BQ-788处理后冠状动脉血管传导率和左心室dP/dt降低，而BQ-123处理后恢复正常。在这三组动物中，再灌注期间乙酰胆碱（3 - 100 ng）和硝普钠（1 - 10 μg）的冠状动脉效应与对照时相同。在完全闭塞后的再灌注期间，生理盐水处理后冠状动脉血管传导率和左心室dP/dt降低，而BQ-123或BQ-788处理后恢复正常。在这三组动物中，再灌注期间生理盐水处理后乙酰胆碱的冠状动脉效应降低但硝普钠的效应未降低，而BQ-123或BQ-788处理后效应逆转。因此，内皮素ET(B)和ET(A)受体的选择性拮抗剂可能对严重缺血后的冠状动脉血管和心肌再灌注产生类似的保护作用。与内皮素ET(A)受体拮抗剂相反，内皮素ET(B)受体的选择性拮抗剂对轻度缺血后的冠状动脉血管和心肌再灌注可能无保护作用。
