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 [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.
Nambi
P
P
Department of Renal Pharmacology, SmithKline Beecham Pharmaceuticals, King of Prussia, Pennsylvania.
Pullen
M
M
Jugus
M
M
Gellai
M
M
D058186:Acute Kidney Injury / Q000209:etiology / Q000378:metabolism*; D000818:Animals; D001806:Blood Urea Nitrogen; D003404:Creatinine / Q000097:blood; D004195:Disease Models, Animal; D016232:Endothelins / Q000378:metabolism; D007457:Iodine Radioisotopes; D007511:Ischemia / Q000150:complications / Q000378:metabolism*; D007668:Kidney / Q000098:blood supply* / Q000648:ultrastructure; D007700:Kinetics; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D017466:Receptors, Endothelin / Q000378:metabolism*
D016232:Endothelins; D007457:Iodine Radioisotopes; D017466:Receptors, Endothelin; D003404:Creatinine