Nitroglycerin-induced desensitization of vascular smooth muscle may be mediated through cyclic GMP-disinhibition of phosphatidylinositol hydrolysis.

The purpose of this study was to investigate the hypothesis that nitroglycerin-induced desensitization of vascular smooth muscle is mediated through cyclic GMP-disinhibition of phosphatidylinositol hydrolysis. Norepinephrine-induced contraction and increased levels of inositol monophosphate, a measure of phosphatidylinositol hydrolysis, in rat aorta. Prior treatment with nitroglycerin inhibited both the norepinephrine-induced contraction and the elevated levels of inositol monophosphate to the same relative magnitude. The nitroglycerin-induced inhibition of contraction and inositol monophosphate formation were prevented in tissues desensitized with nitroglycerin. These results suggest that: nitroglycerin may inhibit vascular smooth muscle contraction through cyclic GMP-inhibition of phosphatidylinositol hydrolysis and desensitization to the relaxant effects of nitroglycerin may be due to disinhibition of the hydrolysis.