Endothelin-1 induces vasoconstriction and nitric oxide release via endothelin ET(B) receptors in isolated perfused rat liver

Eur J Pharmacol. 1997 Jun 11;328(2-3):175-82. doi: 10.1016/s0014-2999(97)83043-9.

Abstract

Endothelin-1 (0.1, 1 and 10 nM) induced a significant increase in portal pressure and nitric oxide (NO) release in the isolated rat liver. The endothelin ET(B) receptor agonist, IRL 1620 (Suc-[Glu9,Ala(11,15)]endothelin-1-(8-21)) (0.1, 1 and 10 nM) also elicited a marked increase in portal pressure and NO release. The potency of endothelin-1 was higher than that of IRL 1620. The endothelin ET(A) receptor antagonist, BQ-123 (cyclo(-D-Trp-D-Asp-Pro-D-Val-Leu)) (1 and 10 microM), had no effect on the endothelin-1-induced change in portal pressure and NO current. In contrast, the endothelin ET(B) receptor antagonist, BQ-788 (N-cis-2,6-dimethylpiperidinocarbonyl-L-gamma-methyl-leucyl-D-1-++ +methoxycarbonyltryptophanyl-D-norleucine) (1 and 10 nM), attenuated the endothelin-1-induced change in portal pressure and NO current. Administration of N(G)-monomethyl-L-arginine (L-NMMA), a NO synthase inhibitor, completely abolished the endothelin-1- or IRL 1620-induced NO release. L-NMMA enhanced the increase in portal pressure and decrease in O2 consumption caused by endothelin-1. These results indicated that endothelin ET(B) receptors mediate both vasoconstriction and NO release and that NO plays a significant role in stabilizing microcirculation in isolated perfused rat liver.

MeSH terms

  • Animals
  • Endothelin Receptor Antagonists
  • Endothelin-1 / pharmacology*
  • Endothelins / pharmacology
  • In Vitro Techniques
  • Liver / drug effects
  • Liver / metabolism*
  • Male
  • Nitric Oxide / metabolism*
  • Oligopeptides / pharmacology
  • Oxygen Consumption / drug effects
  • Peptide Fragments / pharmacology
  • Peptides, Cyclic / pharmacology
  • Piperidines / pharmacology
  • Portal Pressure / drug effects
  • Rats
  • Rats, Sprague-Dawley
  • Receptor, Endothelin B
  • Receptors, Endothelin / drug effects
  • Receptors, Endothelin / metabolism
  • Receptors, Endothelin / physiology*
  • Vasoconstriction / drug effects*
  • omega-N-Methylarginine / pharmacology

Substances

  • Endothelin Receptor Antagonists
  • Endothelin-1
  • Endothelins
  • Oligopeptides
  • Peptide Fragments
  • Peptides, Cyclic
  • Piperidines
  • Receptor, Endothelin B
  • Receptors, Endothelin
  • IRL 1620
  • omega-N-Methylarginine
  • Nitric Oxide
  • BQ 788
  • cyclo(Trp-Asp-Pro-Val-Leu)