Nambi P, Pullen M, Jugus M, Gellai M
Department of Renal Pharmacology, SmithKline Beecham Pharmaceuticals, King of Prussia, Pennsylvania.
J Pharmacol Exp Ther. 1993 Jan;264(1):345-8.
The current study was designed to assess the possible changes in kidney endothelin (ET) receptors in a model of ischemia-induced acute renal failure. In unilaterally nephrectomized (right kidney) Sprague-Dawley rats, the left renal artery was occluded for 30 min under pentobarbital anesthesia (40 mg/kg i.p.). Body temperature was maintained at 37 degrees C. Sham-operated rats were used as control. Plasma creatinine levels were measured and ET receptors were quantitated by binding of [125I]ET-1 to membranes prepared from the renal cortex at 0, 2, 5 and 24 hr after reperfusion. There was a time-dependent increase in plasma creatinine levels as well as in [125I]ET-1 binding to cortical membranes at 2, 5 and 24 hr postreperfusion. Saturation binding experiments using [125I]ET-1 and [125I]ET-3 indicated that this increase in binding was due to an increase in affinity without significant change in maximum binding. The affinities were 219, 134, 100, 69 and 80 pM for [125I]ET-1 and 320, 273, 130, 168 and 80 pM for [125I]ET-3 and, for sham, 0, 2, 5 and 24 hr postreperfusion, respectively. These data support the hypothesis of ET involvement in the pathophysiology of acute renal failure in rats.
本研究旨在评估缺血诱导的急性肾衰竭模型中肾内皮素（ET）受体的可能变化。在单侧肾切除（右肾）的Sprague-Dawley大鼠中，在戊巴比妥麻醉（腹腔注射40mg/kg）下将左肾动脉闭塞30分钟。体温维持在37摄氏度。假手术大鼠用作对照。在再灌注后0、2、5和24小时，测量血浆肌酐水平，并通过[125I]ET-1与从肾皮质制备的膜的结合来定量ET受体。再灌注后2、5和24小时，血浆肌酐水平以及[125I]ET-1与皮质膜的结合呈时间依赖性增加。使用[125I]ET-1和[125I]ET-3的饱和结合实验表明，这种结合增加是由于亲和力增加，最大结合无显著变化。[125I]ET-1的亲和力分别为219、134、100、69和80pM，[125I]ET-3的亲和力分别为320、273、130、168和80pM，假手术组再灌注后0、2、5和24小时的亲和力分别为上述值。这些数据支持ET参与大鼠急性肾衰竭病理生理学的假说。
