Role of cyclic-GMP in relaxations of vascular smooth muscle.
Relaxation of rat aorta segments with sodium nitroprusside and endothelium-dependent vasodilators, such as acetylcholine, histamine, A23187, ATP, thrombin, and trypsin, is associated with cyclic-GMP (cGMP) accumulation in a concentration- and time-dependent fashion. With rat aorta segments, these agents also increase cyclic GMP-dependent protein-kinase activity and alter the incorporation of 32P into numerous smooth-muscle proteins. Identical patterns of protein phosphorylation were observed with both classes of relaxants on two-dimensional gel electrophoresis and autoradiography. The effects of nitroprusside were observed with or without the endothelium present. In contrast, the effects of the endothelium-dependent agents on all of these parameters (cGMP, cGMP-dependent protein kinase and protein phosphorylation) required the integrity of the endothelium. Various inhibitors of phospholipase and lypoxygenase prevented the effects of the endothelium-dependent agents, suggesting that a metabolite of arachidonic acid is the endothelium-relaxant factor and responsible for guanylate-cyclase activation. A smooth-muscle protein with decreased 32P incorporation after treatment with either class of relaxants has been identified as myosin light chain. A model is presented suggesting that the effects of endothelium-dependent vasodilators and directly acting nitrovasodilators converge at the level of guanylate-cyclase activation and cGMP accumulation, which explains the common biochemical and physiological effects on smooth muscle of these two classes of vasodilators.
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Murad
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Rapoport
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Fiscus
D000818:Animals; D006152:Cyclic GMP / Q000032:analysis / Q000502:physiology*; D006162:Guanylate Cyclase / Q000032:analysis; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000502:physiology*; D009599:Nitroprusside / Q000494:pharmacology; D010766:Phosphorylation; D011494:Protein Kinases / Q000032:analysis; D011506:Proteins / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D014664:Vasodilation / Q000187:drug effects*
D011506:Proteins; D009599:Nitroprusside; D011494:Protein Kinases; D006162:Guanylate Cyclase; D006152:Cyclic GMP