Hypoxic coronary vasodilatation and cGMP overproduction are blocked by a nitric oxide synthase inhibitor, but not by a guanylyl cyclase ANF receptor antagonist

Eur J Pharmacol. 1994 Apr 11;256(1):99-102. doi: 10.1016/0014-2999(94)90622-x.

Abstract

Myocardial hypoxia is known to be accompanied by the release of atrial natriuretic factor (ANF), a peptide which dilates the coronary vessels by stimulating particulate guanylyl cyclase. We have assessed whether ANF plays a paracrine role in hypoxic coronary vasodilatation, a reaction which we had previously found to be associated with increased cyclic GMP production. Compound HS 142-1 (100 micrograms/ml), a specific antagonist of the guanylyl cyclase ANF receptor, inhibited by 50-70% the coronary-vasodilating effects of human ANF (1-10 micrograms) administered to isolated guinea pig hearts, but affected neither hypoxic coronary vasodilation nor cyclic GMP overflow. In contrast, the nitric oxide synthase inhibitor N omega-methyl-L-arginine (300 microM) reduced hypoxic coronary vasodilatation and cyclic GMP overproduction by approximately 70% and 50-60%, respectively. Thus, unlike nitric oxide, ANF appears not to play a paracrine role in hypoxic coronary vasodilatation.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Oxidoreductases / antagonists & inhibitors*
  • Animals
  • Arginine / analogs & derivatives
  • Arginine / pharmacology
  • Atrial Natriuretic Factor / antagonists & inhibitors*
  • Coronary Circulation / drug effects
  • Coronary Circulation / physiology*
  • Cyclic GMP / biosynthesis*
  • Guanylate Cyclase / antagonists & inhibitors*
  • Guinea Pigs
  • Humans
  • Hypoxia / metabolism
  • Hypoxia / physiopathology*
  • In Vitro Techniques
  • Male
  • Nitric Oxide / antagonists & inhibitors
  • Nitric Oxide Synthase
  • Perfusion
  • Polysaccharides / pharmacology
  • Receptors, Atrial Natriuretic Factor / antagonists & inhibitors*
  • Receptors, Atrial Natriuretic Factor / drug effects
  • Vasodilation / drug effects
  • Vasodilation / physiology*
  • omega-N-Methylarginine

Substances

  • HS 142-1
  • Polysaccharides
  • omega-N-Methylarginine
  • Nitric Oxide
  • Atrial Natriuretic Factor
  • Arginine
  • Nitric Oxide Synthase
  • Amino Acid Oxidoreductases
  • Guanylate Cyclase
  • Receptors, Atrial Natriuretic Factor
  • Cyclic GMP