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.