title: Endothelium-dependent and nitrovasodilator-induced activation of cyclic GMP-dependent protein kinase in rat aorta.
abstract: Cyclic GMP-dependent protein kinase (cyclic GMP-kinase) activity in isolated strips of rat aorta was measured in the absence and presence of exogenous cyclic GMP (2 microM) and expressed as a ratio. This activity ratio represented an estimate of the endogenous activation state of the enzyme. Acetylcholine [10 microM), an endothelium-dependent vasodilator, increased the activity ratio from a control value of 0.42 to 0.71 in aorta with endothelium intact. With endothelium removed, acetylcholine had no effect on cyclic GMP-kinase activity. The nitrovasodilator sodium nitroprusside (50 nM) increased activity ratios in aorta both with (0.42 to 0.54) and without (0.29 to 0.40) endothelium. Since activity ratios were higher in aortas with an intact endothelium, a tonic influence of the endothelium on aorta cyclic GMP-kinase is suggested. The vasodilator isoproterenol (3 microM) had no effect on cyclic GMP-kinase activity ratios. The increases in cyclic GMP-kinase activity caused by sodium nitroprusside and acetylcholine were preserved when aortas were homogenized in buffer containing 3 mg/ml charcoal. Thus, most of the cyclic GMP-kinase activation occurred in the intact tissue and not because of endogenous cyclic nucleotides present during homogenization or assay. The increases in the activity ratio to sodium nitroprusside and acetylcholine correlate with increases in cyclic GMP concentration and with smooth muscle relaxation. It is concluded that cyclic GMP-kinase in rat aorta is activated by acetylcholine in an endothelium-dependent manner and by sodium nitroprusside in an endothelium-independent manner. These data are consistent with the hypothesis that cyclic GMP mediates relaxation of vascular smooth muscle to acetylcholine and sodium nitroprusside by activating cyclic GMP-kinase and consequent protein phosphorylation. The data further illustrate the importance of endothelial cells in vascular responses to acetylcholine.
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000378:metabolism*; D006152:Cyclic GMP / Q000378:metabolism / Q000494:pharmacology; D004727:Endothelium / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D005292:Ferricyanides / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects; D009599:Nitroprusside / Q000494:pharmacology*; D011494:Protein Kinases / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains
chemical_list: D005292:Ferricyanides; D009599:Nitroprusside; D011494:Protein Kinases; D006152:Cyclic GMP; D000109:Acetylcholine