Effects of endothelin on renal function in dogs and rats

• Published in: American journal of physiology. Renal physiology Vol. 258; no. 4 Pt 2; pp. F775 - F780
• Main Author: Banks, R O
• Format: Journal Article
• Language: English
• Published: United States 01.04.1990
• Subjects: Angiotensin II - analogs & derivatives; Angiotensin II - antagonists & inhibitors; Angiotensin II - pharmacology; Animals; Captopril - pharmacology; Dogs; Dose-Response Relationship, Drug; Endothelins; Endothelium, Vascular - metabolism; Female; Infusions, Intravenous; Injections, Intra-Arterial; Kidney - drug effects; Kidney - physiology; Male; Peptides - pharmacology; Rats; Rats, Inbred Strains; Renal Artery; Saralasin - pharmacology
• ISSN: 0002-9513; 1931-857X; 2163-5773; 1522-1466
• DOI: 10.1152/ajprenal.1990.258.4.F775

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.