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1 Vascular Biology Research Group, Robarts Research Institute, London, Canada
2 Cell Biology Research Group, Robarts Research Institute, London, Canada
3 Vascular Biology Research Group, Robarts Research Institute, Canada
It has been increasingly appreciated that aldosterone elicits acute vascular effects through non-genomic signalling pathways. Our previous studies demonstrated that aldosterone attenuated phenylephrine-mediated constriction in intact vessels (via PI3 kinase-dependent NOS activation) but enhanced vasoconstrictor responses in endothelium-denuded arteries. To determine the mechanism of this vasoconstrictor response, we assessed the effect of aldosterone on myosin light chain phosphorylation and contraction in clonal adult human vascular smooth muscle cells. Acute aldosterone exposure mediated dose-dependent myosin light chain phosphorylation, inhibited by spironolactone and PI3 kinase inhibition. These rapid effects of aldosterone were mimicked by estradiol and hydrocortisone and were also inhibitable by both spironolactone and eplerenone. Paralleling its effects on myosin light chain phosphorylation, aldosterone mediated dose-dependent contraction response that was inhibited by spironolactone. Comparable contractile responses were seen with both 17
-estradiol and hydrocortisone.
In total, these data are consistent with a mechanism of acute aldosterone-mediated contraction common to both glucocorticoids and estrogen. Steroid-mediated vasoconstriction may represent an important pathobiological mechanism of vascular disease- especially in the setting of pre-existing endothelial dysfunction.
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