Aldosterone regulates vascular reactivity: short-term effects mediated by phosphatidylinositol 3-kinase-dependent nitric oxide synthase activation.
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.


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.
Liu
Selina L
SL
Department of Physiology and Pharmacology, University of Western Ontario, London, Ontario, Canada.
Schmuck
Saskia
S
Chorazcyzewski
Jozef Z
JZ
Gros
Robert
R
Feldman
Ross D
RD
D000450:Aldosterone / Q000494:pharmacology*; D000818:Animals; D001011:Aorta; D002417:Cattle; D002478:Cells, Cultured / Q000187:drug effects / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000502:physiology; D004789:Enzyme Activation / Q000187:drug effects; D066298:In Vitro Techniques; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D008297:Male; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D052250:Nitric Oxide Synthase Type III; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology*; D051381:Rats; D011918:Rats, Inbred SHR; D017208:Rats, Wistar; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000378:metabolism; D014655:Vascular Resistance / Q000187:drug effects / Q000502:physiology; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology
D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D000450:Aldosterone; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; D019869:Phosphatidylinositol 3-Kinases; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases