Hypoxic coronary vasodilatation and cGMP overproduction are blocked by a nitric oxide synthase inhibitor, but not by a guanylyl cyclase ANF receptor antagonist.
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.
Park
K H
KH
Department of Pharmacology, Cornell University Medical College, New York, NY 10021.
Levi
R
R
D000594:Amino Acid Oxidoreductases / Q000037:antagonists & inhibitors*; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D009320:Atrial Natriuretic Factor / Q000037:antagonists & inhibitors*; D003326:Coronary Circulation / Q000187:drug effects / Q000502:physiology*; D006152:Cyclic GMP / Q000096:biosynthesis*; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors*; D006168:Guinea Pigs; D006801:Humans; D000860:Hypoxia / Q000378:metabolism / Q000503:physiopathology*; D066298:In Vitro Techniques; D008297:Male; D009569:Nitric Oxide / Q000037:antagonists & inhibitors; D019001:Nitric Oxide Synthase; D010477:Perfusion; D011134:Polysaccharides / Q000494:pharmacology; D017461:Receptors, Atrial Natriuretic Factor / Q000037:antagonists & inhibitors* / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*; D019323:omega-N-Methylarginine
C072551:HS 142-1; D011134:Polysaccharides; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D009320:Atrial Natriuretic Factor; D001120:Arginine; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; D006162:Guanylate Cyclase; D017461:Receptors, Atrial Natriuretic Factor; D006152:Cyclic GMP