title: Regulation of aldosterone synthase in human vascular endothelial cells by angiotensin II and adrenocorticotropin.
abstract: Mineralocorticoids have been suggested to act on blood vessels, leading to increased vasoreactivity and peripheral resistance. Aldosterone is synthesized locally in blood vessels and participates in the hypertrophy of vascular smooth muscle cells. In this study we examined the effects of angiotensin II (ANG II), potassium, and ACTH on the production of aldosterone, the activity of aldosterone synthase, and the expression of CYP11B2 and CYP11B1 messenger ribonucleic acid (mRNA) in cultured human vascular endothelial cells. Human vascular endothelial cells were incubated with ANG II, potassium, or ACTH with or without [14C]deoxycorticosterone ([14C]DOC). Incubation medium was collected, and chromatography was preformed in a reverse phase high performance liquid chromatography system. The concentration of aldosterone in the incubation medium was measured using RIA after separation with the high performance liquid chromatography system. The activity of aldosterone synthase was estimated by the conversion of [14C]DOC to [14C]aldosterone. The levels of CYP11B2 and CYP11B1 mRNA were determined by competitive PCR. ANG II, potassium, and ACTH increased the production levels of aldosterone in a dose-dependent fashion. Both ANG II and potassium increased the conversion of [14C]DOC to [14C]aldosterone, but ACTH did not significantly increase the conversion. Both ANG II and potassium increased the concentration of CYP11B2 mRNA, but not that of CYP11B1 mRNA. Tumor necrosis factor reduced ANG II- and potassium-induced aldosterone synthesis and CYP11B2 mRNA levels. ACTH did not influence the expression of CYP11B2 mRNA. These results suggest that vascular aldosterone synthase is controlled by ANG II and potassium at the transcriptional level.
authors.affiliation: Second Department of Internal Medicine, Kanazawa University School of Medicine, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Takeda
authors.forename: I
authors.initials: I
authors.lastname: Miyamori
authors.forename: T
authors.initials: T
authors.lastname: Yoneda
authors.forename: H
authors.initials: H
authors.lastname: Hatakeyama
authors.forename: S
authors.initials: S
authors.lastname: Inaba
authors.forename: K
authors.initials: K
authors.lastname: Furukawa
authors.forename: H
authors.initials: H
authors.lastname: Mabuchi
authors.forename: R
authors.initials: R
authors.lastname: Takeda
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000494:pharmacology*; D000450:Aldosterone / Q000096:biosynthesis; D000804:Angiotensin II / Q000494:pharmacology*; D002478:Cells, Cultured; D019405:Cytochrome P-450 CYP11B2 / Q000235:genetics / Q000378:metabolism*; D003900:Desoxycorticosterone / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology*; D006801:Humans; D011188:Potassium / Q000494:pharmacology; D012333:RNA, Messenger / Q000037:antagonists & inhibitors / Q000378:metabolism; D013252:Steroid 11-beta-Hydroxylase / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D000804:Angiotensin II; D003900:Desoxycorticosterone; D000450:Aldosterone; D000324:Adrenocorticotropic Hormone; D019405:Cytochrome P-450 CYP11B2; D013252:Steroid 11-beta-Hydroxylase; D011188:Potassium