Circulation. 2003;108:2400-2406
Published online before print October 13, 2003, doi: 10.1161/01.CIR.0000093188.53554.44
Published online before print October 13, 2003, doi: 10.1161/01.CIR.0000093188.53554.44
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(Circulation. 2003;108:2400.)
© 2003 American Heart Association, Inc.
Basic Science Reports |
Aldosterone Regulates Vascular Reactivity
Short-Term Effects Mediated by Phosphatidylinositol 3-Kinase–Dependent Nitric Oxide Synthase Activation
From the Departments of Physiology and Pharmacology (S.L.L., R.D.F.) and of Medicine (R.G., R.D.F.), University of Western Ontario, London, and the Robarts Research Institute (S.L.L., S.S., J.Z.C., R.G., R.D.F.), London, Ontario, Canada.
Correspondence to Dr Ross D. Feldman, Robarts Research Institute, PO Box 5015, 100 Perth Dr, London, Ontario, Canada N6A 5K8. E-mail feldmanr{at}lhsc.on.ca
Received September 30, 2002; de novo received March 31, 2003; revision received July 9, 2003; accepted July 10, 2003.
Background— There is increasing evidence for rapid nongenomic effects of aldosterone. Therefore, we studied the immediate effects of aldosterone on vascular reactivity in rat aortic ring segments and on endothelial and vascular smooth muscle cellular responses.
Methods and Results— In endothelium-intact ring segments, aldosterone attenuated phenylephrine-mediated constriction (maximal reduction, 25±4% below control phenylephrine-mediated constriction). In contrast, in endothelium-denuded vessels, aldosterone mediated a monophasic dose-dependent enhancement of vasoconstrictor response. In endothelial cells, aldosterone caused a phosphatidylinositol 3-kinase (PI3K)–dependent increase in nitric oxide synthase activity as well as PI3K-dependent activation of extracellular signal–regulated kinase 1/2 and p70 S6 kinase.
Conclusions— Overall, these data support a novel effect of aldosterone on vascular endothelial and smooth muscle cell function. These rapid effects of aldosterone might be important in both the short- and long-term regulation of peripheral vascular resistance. Furthermore, in the setting of endothelial dysfunction, alterations in aldosterone’s short-term vascular responses might contribute to its pathophysiological effects in cardiovascular disease.
Key Words: arteries • endothelium • hormones • vasodilation
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