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.
D000818:Animals; D001011:Aorta; D006152:Cyclic GMP / Q000502:physiology*; D004361:Drug Tolerance; D006868:Hydrolysis; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D005996:Nitroglycerin / Q000494:pharmacology*; D009638:Norepinephrine / Q000494:pharmacology; D010716:Phosphatidylinositols / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains
D010716:Phosphatidylinositols; D005996:Nitroglycerin; D006152:Cyclic GMP; D009638:Norepinephrine