Effects of endothelin on renal function in dogs and rats.
Endothelin was infused for 20 min into the left renal artery of pentobarbital-anesthetized dogs at 1 (n = 6) and 10 (n = 5) ng.min-1.kg-1. Renal blood flow (flow probe) increased 6 +/- 2 (SE) and 29 +/- 2% during the first 5 min of endothelin infusion and then slowly decreased to 86 +/- 3 and 29 +/- 2% of control at 20 min, respectively; the low renal blood flow persisted for at least 30 min after endothelin infusion, and there were no systemic effects of the peptide at either dose. These effects of endothelin on renal function were not altered by the angiotensin (ANG) II receptor antagonist, [Sar1,Thr8]ANG II. In the rat, endothelin was infused intravenously into three groups of pentobarbital-anesthetized females for 30 min at 0.1 microgram.min-1.kg-1; five had endothelin only, six had either endothelin + [Sar1,Thr8]ANG II (n = 4, 1.0 micrograms.min-1.kg-1) or endothelin + saralasin (n = 2, 1 and 2 micrograms.kg-1.min-1), and five had endothelin + captopril (5 mg.h-1.kg-1). The inhibitors were infused throughout the entire experiment. During infusion of endothelin alone mean arterial blood pressure increased from 106 +/- 2 to 136 +/- 4 mmHg and the glomerular filtration rate decreased from 2.7 +/- 0.2 to 0.7 +/- 0.3 ml/min. Captopril attenuated the endothelin-induced changes in renal function but not the increase in mean arterial blood pressure, whereas the competitive ANG II receptor antagonists had no effect on either the systemic or renal actions of the peptide. These data demonstrate that endothelin is a potent renal vasoconstrictor with transient vasodilator effects and that the inhibition of kinin degradation may attenuate the renal actions of the peptide.
Banks
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Department of Physiology and Biophysics, University of Cincinnati, Ohio 45267-0576.
D000804:Angiotensin II / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000494:pharmacology; D000818:Animals; D002216:Captopril / Q000494:pharmacology; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D016232:Endothelins; D004730:Endothelium, Vascular / Q000378:metabolism; D005260:Female; D007262:Infusions, Intravenous; D007269:Injections, Intra-Arterial; D007668:Kidney / Q000187:drug effects* / Q000502:physiology; D008297:Male; D010455:Peptides / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012077:Renal Artery; D012504:Saralasin / Q000494:pharmacology
D016232:Endothelins; D010455:Peptides; D000804:Angiotensin II; C014805:angiotensin II, Sar(1)-Thr(8)-; D002216:Captopril; D012504:Saralasin