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(Hypertension. 1995;25:752-757.)
© 1995 American Heart Association, Inc.
Articles |
Calcium- and Protein Kinase C–Dependent Basal Tone in the Aorta of Hypertensive Rats
From the Department of Pharmacology, New York Medical College, Valhalla.
Abstract We examined the regulatory influence of nitric oxide on development of calcium- and protein kinase C–dependent basal tone in rings of thoracic aortas from rats with aortic coarctation–induced hypertension and from normotensive controls. Aortic rings from hypertensive rats but not those from normotensive rats, bathed in Krebs' bicarbonate buffer and subjected to 2 g of passive stretch, were relaxed by removal of calcium from the buffer and by the protein kinase C inhibitors staurosporine and calphostin C. Protein kinase C activity was much greater in homogenates of aortae from hypertensive rats than in those from normotensive controls (2124±785 versus 608±73 pmol · min-1 · mg protein-1, respectively). Relaxant responses to removal of calcium and to staurosporine were greater in aortic rings rubbed to remove the vascular endothelium than in endothelium-intact rings (-1.07±0.12 versus -0.70±0.10 g tension/mg tissue, respectively, for calcium removal and -1.10±0.12 versus -0.65±0.08 g tension/mg tissue, respectively, for staurosporine). Treatment with an inhibitor of nitric oxide synthesis increased calcium-dependent tone in both intact and endothelium-denuded aortic rings from hypertensive rats. Conversely, the administration of sodium nitroprusside or L-arginine reversed tone in both intact and denuded aortic rings from hypertensive rats, but acetylcholine reversed tone only in intact rings. The relaxant effects of these agents were paralleled by increases in cyclic guanosine monophosphate in aortic tissue. We conclude that aortic rings from rats with aortic coarctation–induced hypertension display calcium-dependent, protein kinase C–mediated tone in the absence of exogenous vasoconstrictors. Furthermore, endogenous nitric oxide from endothelial and nonendothelial sources suppresses the development of this tone.
Key Words: hypertension, arterial • muscle, smooth, vascular • nitric oxide • protein kinase C • calcium • vasoconstriction
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