P-495: Aldosterone regulation of vascular tone via immediate effects on endothelial function

• Published in: American journal of hypertension 2002-04, Vol.15 (S3), p.212A-212A
• Main Authors: Liu, Selina L., Schmuck, Saskia, Parker, Shannon K., Dixon, S.Jeffrey, Feldman, Ross D.
• Format: Article
• Language: English
• Subjects: Aldosterone; Endothelial; Nitric Oxide
• ISSN: 0895-7061; 1941-7225; 1879-1905
• DOI: 10.1016/S0895-7061(02)02846-7

The effects of aldosterone are typically ascribed to the activation of an intracellular receptor that mediates its effects by regulating expression of target genes. In addition to genomic effects, however, there is increasing evidence for rapid, non-genomic effects. The acute effect of aldosterone on vascular tone was unknown. Therefore, we studied the immediate effects of aldosterone on alpha-adrenoceptor-mediated function in aortic ring segments from 10-week-old male Wistar Rats and in primary bovine aortic endothelial cell (BAEC) cultures. Ring segments were incubated (2 min) with aldosterone followed by administration of a submaximal constricting dose of phenylephrine (100 nM). Aldosterone (1 pM-100 nM) caused a biphasic attenuation of phenylephrine-mediated vasoconstriction in endothelium-intact preparations (to a maximal reduction of 25±4% of control phenylephrine-mediated constriction at an aldosterone concentration of 10 pM). In contrast, in endothelial-denuded vessels, aldosterone mediated a monophasic dose-dependent enhancement of vasoconstrictor response (Emax: 24±4% above control, EC50: 0.57±0.6 pM, n=5). Further, in endothelium-intact vessels, L-NMMA (10 μM) blocked the effect of aldosterone to attenuate vasoconstriction, suggesting that the effect of aldosterone was NO synthase-dependent. In BAEC, aldosterone caused an increase in MAP kinase (ERK1/2) and p70 S6 kinase phosphorylation by 10 pM. Cytosensor analysis showed that aldosterone treatment did not affect H+ flux. Overall, these data support a novel non-genomic endothelial-dependent effect of aldosterone paralleling ERK1/2 and p70 S6 kinase activation, which could be important in acute regulation of peripheral vascular resistance.