title: Aldosterone Impairs Vascular Smooth Muscle Function: From Clinical to Bench Research.
abstract: BACKGROUND
  The effect of aldosterone on vascular smooth muscle cell function is still unclear. One method to measure vascular smooth muscle cell function is endothelial-independent vascular dilation, for which the key factor is sarcoplasmic reticulum calcium adenosine triphosphatase (SERCA).
  
  
  OBJECTIVE
  Our objective was to investigate the effect of aldosterone on vascular smooth muscle cell function and SERCA regulation.
  
  
  METHODS
  We prospectively analyzed 35 patients with primary aldosteronism (PA; 32 patients with aldosterone-producing adenoma and three patients with idiopathic hyperaldosteronism) and 30 patients with essential hypertension (EH) who were enrolled as the control group. Flow and nitrate-mediated dilation were performed in both groups and 1 year after adrenalectomy in the patients with aldosterone-producing adenoma. In addition, we investigated the effect of aldosterone on SERCA regulation in human aortic smooth muscle cells.
  
  
  METHODS
  This study took place in an academic clinical research center.
  
  
  METHODS
  Participants included 35 patients with PA and 30 patients with EH.
  
  
  METHODS
  Adrenalectomy was undertaken in patients with aldosterone-producing adenoma.
  
  
  RESULTS
  The PA patients had significantly lower flow-mediated dilation (FMD) and nitrate-mediated dilation (NMD) values than the patients with EH (FMD: 13 ± 6 vs 16 ± 4; NMD: 16 ± 6 vs 19 ± 5; both P < .05). FMD/NMD were significantly correlated with log 24 hour-urine aldosterone (FMD: r = -0.287, P = .048; NMD: r = -0.402, P = .005) but not blood pressure. The impaired FMD and NMD values were significantly restored 1 year after adrenalectomy (FMD: 11 ± 4 to 19 ± 7; NMD: 15 ± 6 to 21 ± 6; both P < .01). Under confocal microscopy, aldosterone was shown to suppress the expression of SERCA2a of human aortic smooth muscle cells. Aldosterone significantly suppressed the expression of SERCA2a from 10(-8) M in mRNA and protein levels. This suppression was through down-regulation of mineralocorticoid receptor dependent mitochondrial transcription factors A and B2.
  
  
  CONCLUSIONS
  Aldosterone impairs vascular smooth muscle cell function and suppresses SERCA 2a expression.
authors.affiliation: Departments of Obstetrics and Gynecology (C.-H.C.) and Internal Medicine (Y.-H.C., C.-S.H., Y.-L.T., V.-C.W., C.-T.T., C.-K.W., Y.-L.H. K.-D.W., Y.-H.L.), National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan; Cardiology Division of Cardiovascular Medical Center (Y.-Y.C.), Far Eastern Memorial Hospital, New Taipei City, Taiwan; and Department of Internal Medicine (X.-M.W.), Taoyuan General Hospital, Taoyuan, Taiwan.
authors.forename: Chia-Hung
authors.initials: CH
authors.lastname: Chou
authors.affiliation: Departments of Obstetrics and Gynecology (C.-H.C.) and Internal Medicine (Y.-H.C., C.-S.H., Y.-L.T., V.-C.W., C.-T.T., C.-K.W., Y.-L.H. K.-D.W., Y.-H.L.), National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan; Cardiology Division of Cardiovascular Medical Center (Y.-Y.C.), Far Eastern Memorial Hospital, New Taipei City, Taiwan; and Department of Internal Medicine (X.-M.W.), Taoyuan General Hospital, Taoyuan, Taiwan.
authors.forename: Ying-Hsien
authors.initials: YH
authors.lastname: Chen
authors.affiliation: Departments of Obstetrics and Gynecology (C.-H.C.) and Internal Medicine (Y.-H.C., C.-S.H., Y.-L.T., V.-C.W., C.-T.T., C.-K.W., Y.-L.H. K.-D.W., Y.-H.L.), National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan; Cardiology Division of Cardiovascular Medical Center (Y.-Y.C.), Far Eastern Memorial Hospital, New Taipei City, Taiwan; and Department of Internal Medicine (X.-M.W.), Taoyuan General Hospital, Taoyuan, Taiwan.
authors.forename: Chi-Sheng
authors.initials: CS
authors.lastname: Hung
authors.affiliation: Departments of Obstetrics and Gynecology (C.-H.C.) and Internal Medicine (Y.-H.C., C.-S.H., Y.-L.T., V.-C.W., C.-T.T., C.-K.W., Y.-L.H. K.-D.W., Y.-H.L.), National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan; Cardiology Division of Cardiovascular Medical Center (Y.-Y.C.), Far Eastern Memorial Hospital, New Taipei City, Taiwan; and Department of Internal Medicine (X.-M.W.), Taoyuan General Hospital, Taoyuan, Taiwan.
authors.forename: Yi-Yao
authors.initials: YY
authors.lastname: Chang
authors.affiliation: Departments of Obstetrics and Gynecology (C.-H.C.) and Internal Medicine (Y.-H.C., C.-S.H., Y.-L.T., V.-C.W., C.-T.T., C.-K.W., Y.-L.H. K.-D.W., Y.-H.L.), National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan; Cardiology Division of Cardiovascular Medical Center (Y.-Y.C.), Far Eastern Memorial Hospital, New Taipei City, Taiwan; and Department of Internal Medicine (X.-M.W.), Taoyuan General Hospital, Taoyuan, Taiwan.
authors.forename: Yu-Lin
authors.initials: YL
authors.lastname: Tzeng
authors.affiliation: Departments of Obstetrics and Gynecology (C.-H.C.) and Internal Medicine (Y.-H.C., C.-S.H., Y.-L.T., V.-C.W., C.-T.T., C.-K.W., Y.-L.H. K.-D.W., Y.-H.L.), National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan; Cardiology Division of Cardiovascular Medical Center (Y.-Y.C.), Far Eastern Memorial Hospital, New Taipei City, Taiwan; and Department of Internal Medicine (X.-M.W.), Taoyuan General Hospital, Taoyuan, Taiwan.
authors.forename: Xue-Ming
authors.initials: XM
authors.lastname: Wu
authors.affiliation: Departments of Obstetrics and Gynecology (C.-H.C.) and Internal Medicine (Y.-H.C., C.-S.H., Y.-L.T., V.-C.W., C.-T.T., C.-K.W., Y.-L.H. K.-D.W., Y.-H.L.), National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan; Cardiology Division of Cardiovascular Medical Center (Y.-Y.C.), Far Eastern Memorial Hospital, New Taipei City, Taiwan; and Department of Internal Medicine (X.-M.W.), Taoyuan General Hospital, Taoyuan, Taiwan.
authors.forename: Vin-Cent
authors.initials: VC
authors.lastname: Wu
authors.affiliation: Departments of Obstetrics and Gynecology (C.-H.C.) and Internal Medicine (Y.-H.C., C.-S.H., Y.-L.T., V.-C.W., C.-T.T., C.-K.W., Y.-L.H. K.-D.W., Y.-H.L.), National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan; Cardiology Division of Cardiovascular Medical Center (Y.-Y.C.), Far Eastern Memorial Hospital, New Taipei City, Taiwan; and Department of Internal Medicine (X.-M.W.), Taoyuan General Hospital, Taoyuan, Taiwan.
authors.forename: Chia-Ti
authors.initials: CT
authors.lastname: Tsai
authors.affiliation: Departments of Obstetrics and Gynecology (C.-H.C.) and Internal Medicine (Y.-H.C., C.-S.H., Y.-L.T., V.-C.W., C.-T.T., C.-K.W., Y.-L.H. K.-D.W., Y.-H.L.), National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan; Cardiology Division of Cardiovascular Medical Center (Y.-Y.C.), Far Eastern Memorial Hospital, New Taipei City, Taiwan; and Department of Internal Medicine (X.-M.W.), Taoyuan General Hospital, Taoyuan, Taiwan.
authors.forename: Cho-Kai
authors.initials: CK
authors.lastname: Wu
authors.affiliation: Departments of Obstetrics and Gynecology (C.-H.C.) and Internal Medicine (Y.-H.C., C.-S.H., Y.-L.T., V.-C.W., C.-T.T., C.-K.W., Y.-L.H. K.-D.W., Y.-H.L.), National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan; Cardiology Division of Cardiovascular Medical Center (Y.-Y.C.), Far Eastern Memorial Hospital, New Taipei City, Taiwan; and Department of Internal Medicine (X.-M.W.), Taoyuan General Hospital, Taoyuan, Taiwan.
authors.forename: Yi-Lwun
authors.initials: YL
authors.lastname: Ho
authors.affiliation: Departments of Obstetrics and Gynecology (C.-H.C.) and Internal Medicine (Y.-H.C., C.-S.H., Y.-L.T., V.-C.W., C.-T.T., C.-K.W., Y.-L.H. K.-D.W., Y.-H.L.), National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan; Cardiology Division of Cardiovascular Medical Center (Y.-Y.C.), Far Eastern Memorial Hospital, New Taipei City, Taiwan; and Department of Internal Medicine (X.-M.W.), Taoyuan General Hospital, Taoyuan, Taiwan.
authors.forename: Kwan-Dun
authors.initials: KD
authors.lastname: Wu
authors.affiliation: Departments of Obstetrics and Gynecology (C.-H.C.) and Internal Medicine (Y.-H.C., C.-S.H., Y.-L.T., V.-C.W., C.-T.T., C.-K.W., Y.-L.H. K.-D.W., Y.-H.L.), National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan; Cardiology Division of Cardiovascular Medical Center (Y.-Y.C.), Far Eastern Memorial Hospital, New Taipei City, Taiwan; and Department of Internal Medicine (X.-M.W.), Taoyuan General Hospital, Taoyuan, Taiwan.
authors.forename: Yen-Hung
authors.initials: YH
authors.lastname: Lin
mesh_terms: D000315:Adrenalectomy; D000328:Adult; D000450:Aldosterone / Q000494:pharmacology*; D001794:Blood Pressure; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D006929:Hyperaldosteronism / Q000378:metabolism / Q000503:physiopathology* / Q000601:surgery; D008297:Male; D008875:Middle Aged; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects*; D009566:Nitrates / Q000494:pharmacology; D011446:Prospective Studies; D034622:RNA Interference; D012333:RNA, Messenger / Q000096:biosynthesis; D018161:Receptors, Mineralocorticoid / Q000187:drug effects / Q000378:metabolism; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000378:metabolism; D016896:Treatment Outcome; D014664:Vasodilation / Q000187:drug effects*
chemical_list: D009566:Nitrates; D012333:RNA, Messenger; D018161:Receptors, Mineralocorticoid; D000450:Aldosterone; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases