The role of ETB receptors in normotensive and hypertensive rats as revealed by the non-peptide selective ETB receptor antagonist Ro 46-8443

FEBS Lett. 1996 Mar 25;383(1-2):42-5. doi: 10.1016/0014-5793(96)00212-8.

Abstract

We used Ro 46-8443, non-peptidic antagonist selective of endothelin ETB receptors, to study the role of ETB receptors in rat hypertension models. In normotensive rats, Ro 46-8443 decreased blood pressure, but in SHR and DOCA rats, it induced a pressor effect, due to blockade of ETB-mediated release of nitric oxide since L-NAME prevented it. In rats rendered hypertensive by chronic L-NAME, Ro 46-8443 did not induce a pressor but depressor effect. Thus, in DOCA rats and SHR, Ro 46-8443 reveals a predominant influence of endothelial 'vasorelaxant' ETB receptors, while in normotensive rats the prevailing role of ETB receptors seems to be in mediating a vasoconstrictor tone.

MeSH terms

  • Animals
  • Arginine / analogs & derivatives
  • Arginine / pharmacology
  • Blood Pressure* / drug effects
  • Endothelin Receptor Antagonists
  • Hypertension / physiopathology*
  • NG-Nitroarginine Methyl Ester
  • Nitric Oxide Synthase / antagonists & inhibitors
  • Peptides, Cyclic / pharmacology
  • Pyrimidines / pharmacology*
  • Rats
  • Rats, Inbred SHR
  • Rats, Inbred WKY
  • Receptor, Endothelin B
  • Receptors, Endothelin / physiology*
  • Sulfonamides / pharmacology*
  • Viper Venoms / pharmacology

Substances

  • Endothelin Receptor Antagonists
  • Peptides, Cyclic
  • Pyrimidines
  • Receptor, Endothelin B
  • Receptors, Endothelin
  • Ro 46-8443
  • Sulfonamides
  • Viper Venoms
  • sarafotoxins s6
  • Arginine
  • Nitric Oxide Synthase
  • cyclo(Trp-Asp-Pro-Val-Leu)
  • NG-Nitroarginine Methyl Ester