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.