Dissociation of nitrovasodilator-induced relaxation from cyclic GMP levels during in vitro nitrate tolerance.
The effects of nitroglycerin tolerance on relaxation and cyclic GMP accumulation by nitroglycerin, nitric oxide and S-nitroso-N-acetylpenicillamine were examined in isolated rate aortic rings. Cyclic GMP accumulation by nitroglycerin, S-nitroso-N-acetylpenicillamine and nitric oxide was diminished in nitroglycerin-tolerant aorta. In contrast, only relaxation by nitroglycerin, but not S-nitroso-N-acetylpenicillamine and nitric oxide, was attenuated. These data suggest that cyclic GMP levels might represent an inadequate index for mechanistic studies of nitroglycerin relaxation tolerance.
Kowaluk
E A
EA
Department of Pharmaceutics, School of Pharmacy, State University of New York, Buffalo 14260.
Fung
H L
HL
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D006152:Cyclic GMP / Q000378:metabolism*; D004361:Drug Tolerance; D066298:In Vitro Techniques; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D009569:Nitric Oxide / Q000494:pharmacology*; D010396:Penicillamine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D026423:S-Nitroso-N-Acetylpenicillamine; D014665:Vasodilator Agents / Q000494:pharmacology*
D014665:Vasodilator Agents; D009569:Nitric Oxide; D026423:S-Nitroso-N-Acetylpenicillamine; D010396:Penicillamine; D006152:Cyclic GMP