Watts J A, Chapat S, Johnson D E, Janis R A
Department of Biology, University of North Carolina, Charlotte 28223.
J Cardiovasc Pharmacol. 1992 Jun;19(6):929-36. doi: 10.1097/00005344-199206000-00014.
Changes in the vascular response of isolated, perfused rat hearts to endothelin-1 (ET-1) and binding of [125I]ET-1 to cardiac membranes were examined following ischemia (30 min, zero flow) and reperfusion (15 min). Infusion of ET-1 (0, 2.5, 5, 7.5, and 10 x 10(-10) M) increased the control heart perfusion pressure (61, 73, 88, 102, and 117 mm Hg, respectively). Ischemic and reperfused hearts were more sensitive to ET-1 infusion (p less than 0.05 at all concentrations). Nisoldipine (NIS, 1 nM) prevented the rise in sensitivity to ET-1 following ischemia and reperfusion. Two binding sites for [125I]ET-1 were identified in cardiac membranes. High-affinity (Kd = 0.04 nM, Bmax = 0.46 pmol/mg of protein) and low-affinity (Kd = 13.8 nM, Bmax = 5.4 pmol/mg of protein) sites were unchanged by ischemia and reperfusion, and NIS did not change binding constants in control or ischemic and reperfused hearts. Increased ET-1 sensitivity after ischemia may be due to other factors. Endothelium-dependent vasodilation and endothelium-independent vasodilation were significantly reduced following 30 min of ischemia. Inhibition of dilator responses may account for increased ET-1 responses following transient ischemia.
在缺血（30分钟，无血流）和再灌注（15分钟）后，检测了离体灌注大鼠心脏对内皮素-1（ET-1）的血管反应变化以及[125I]ET-1与心脏膜的结合情况。输注ET-1（0、2.5、5、7.5和10×10⁻¹⁰ M）可使对照心脏灌注压升高（分别为61、73、88、102和117 mmHg）。缺血和再灌注后的心脏对ET-1输注更为敏感（所有浓度下p均小于0.05）。尼索地平（NIS，1 nM）可防止缺血和再灌注后对ET-1敏感性的升高。在心脏膜中鉴定出两个[125I]ET-1结合位点。高亲和力（Kd = 0.04 nM，Bmax = 0.46 pmol/mg蛋白质）和低亲和力（Kd = 13.8 nM，Bmax = 5.4 pmol/mg蛋白质）位点在缺血和再灌注后未发生变化，且NIS在对照、缺血和再灌注心脏中均未改变结合常数。缺血后ET-1敏感性增加可能归因于其他因素。缺血30分钟后，内皮依赖性血管舒张和非内皮依赖性血管舒张均显著降低。扩张反应的抑制可能解释了短暂缺血后ET-1反应增加的原因。
