Renal effects of endothelin in anesthetized rabbits

Naoto Ono, Toshiyuki Matsui, Makoto Yoshida, Mizue Suzuki-Kusaba, Hiroaki Hisa, Susumu Satoh

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)

Abstract

Intrarenal arterial infusion of endothelin-1 (1, 3 and 10 ng/kg per min) reduced renal blood flow, urine flow rate and urinary Na+ excretion without affecting fractional Na+ excretion in anesthetized rabbits. An endothelin ET(A) receptor antagonist (R)2-[(R)-2-[(S)-2-[[1-(hexahydro-1H-azepinyl)]carbonyl]amino-4-methyl-pentanoyl]amino-3-[3-(1-methyl-1H-indolyl)]propionyl]amino-3-(2-pyridyl)propionic acid (FR139317, 1 μg/kg per min) attenuated the endothelin-1 (1 ng/kg per min)-induced renal responses. An endothelin ET(B) receptor antagonist N-cis 2,6-dimetylpiperidinocarbonyl-l-γ-metylleucyl-d-1-methoxycarbonyltryptophanyl-d-norleucine (BQ-788, 1 μg/kg per min) potentiated the endothelin-1-induced changes in renal blood flow, urine flow rate and urinary Na+ excretion. A nitric oxide (NO) synthase inhibitor N(ω)-nitro-l-arginine methyl ester (l-NAME, 50 μg/kg per min) also potentiated the endothelin-1-induced reductions in urine flow rate and urinary Na+ excretion but not the reduction in renal blood flow. Endothelin-1 reduced fractional Na+ excretion in the presence of BQ-788 or l-NAME. A spontaneous NO donor 1-hydroxy-2-oxo-3-(N-methyl-3-aminopropyl)-3-methyl-1-triazene (30 ng/kg per min) slightly attenuated the antinatriuresis but not the vasoconstriction induced by endothelin-1. These results suggest that in the rabbit kidney in vivo endothelin ET(A) receptors mediate endothelin-1-evoked vasoconstriction and tubular Na+ reabsorption, that the concomitant stimulation of endothelin ET(B) receptors by endothelin-1 counteracts both the ET(A) receptor-mediated vascular and tubular actions, and that the tubular action, but not the vascular action, of endothelin-1 is also susceptible to changes in renal NO level. Copyright (C) 1998 Elsevier Science B.V.

Original languageEnglish
Pages (from-to)177-184
Number of pages8
JournalEuropean Journal of Pharmacology
Volume359
Issue number2-3
DOIs
Publication statusPublished - 1998 Oct 23

Keywords

  • Endothelin ET(A) receptor
  • Endothelin ET(B) receptor
  • Endothelin-1
  • Kidney
  • Nitric oxide (NO)
  • Rabbit

ASJC Scopus subject areas

  • Pharmacology

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