title: Rapid effects of aldosterone on clonal human vascular smooth muscle cells.
abstract: It has been increasingly appreciated that aldosterone elicits acute vascular effects through nongenomic signaling pathways. Our previous studies demonstrated that aldosterone attenuated phenylephrine-mediated constriction in intact vessels [via phosphatidylinositol 3-kinase-dependent nitric oxide synthase 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 phosphatidylinositol 3-kinase inhibition. These rapid effects of aldosterone were mimicked by estradiol and hydrocortisone and were also inhibitable by both spironolactone and eplerenone. In parallel to its effects on myosin light-chain phosphorylation, aldosterone mediated dose-dependent contraction responses that were inhibited by spironolactone. Comparable contractile responses were seen with both 17beta-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 preexisting endothelial dysfunction.
authors.affiliation: Robarts Research Institute, 100 Perth Dr, London, ON, Canada.
authors.forename: Robert
authors.initials: R
authors.lastname: Gros
authors.forename: Qingming
authors.initials: Q
authors.lastname: Ding
authors.forename: Souzan
authors.initials: S
authors.lastname: Armstrong
authors.forename: Caroline
authors.initials: C
authors.lastname: O'Neil
authors.forename: J Geoffrey
authors.initials: JG
authors.lastname: Pickering
authors.forename: Ross D
authors.initials: RD
authors.lastname: Feldman
mesh_terms: D000450:Aldosterone / Q000494:pharmacology / Q000502:physiology*; D001013:Aorta, Thoracic / Q000166:cytology; D002460:Cell Line; D002999:Clone Cells; D000077545:Eplerenone; D004958:Estradiol; D006801:Humans; D006854:Hydrocortisone / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000502:physiology*; D018994:Myosin Light Chains / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D010766:Phosphorylation; D015398:Signal Transduction; D013148:Spironolactone / Q000031:analogs & derivatives / Q000494:pharmacology; D014661:Vasoconstriction; D014662:Vasoconstrictor Agents / Q000494:pharmacology
chemical_list: D018994:Myosin Light Chains; D014662:Vasoconstrictor Agents; D013148:Spironolactone; D000450:Aldosterone; D004958:Estradiol; D000077545:Eplerenone; D019869:Phosphatidylinositol 3-Kinases; D006854:Hydrocortisone