RAT-KIDNEY ENDOTHELIN RECEPTORS IN ISCHEMIA-INDUCED ACUTE-RENAL-FAILURE

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 [I-125]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 [I-125]ET-1 binding to cortical membranes at 2, 5 and 24 hr postreperfusion. Saturation binding experiments using [I-125]ET-1 and [I-125]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 [I-125]ET-1 and 320, 273, 130, 168 and 80 pM for [I-125]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.