Chia-Hung Chou1, Ying-Hsien Chen1, Chi-Sheng Hung1, Yi-Yao Chang1, Yu-Lin Tzeng1, Xue-Ming Wu1, Vin-Cent Wu1, Chia-Ti Tsai1, Cho-Kai Wu1, Yi-Lwun Ho1, Kwan-Dun Wu1, Yen-Hung Lin1. 1. 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.
Abstract
CONTEXT: 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. DESIGN: 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. SETTING: This study took place in an academic clinical research center. PARTICIPANTS: Participants included 35 patients with PA and 30 patients with EH. INTERVENTIONS: 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.
CONTEXT: 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. DESIGN: 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. SETTING: This study took place in an academic clinical research center. PARTICIPANTS: Participants included 35 patients with PA and 30 patients with EH. INTERVENTIONS: Adrenalectomy was undertaken in patients with aldosterone-producing adenoma. RESULTS: The PApatients 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: Chia-Hui Chang; Stephen Shei-Dei Yang; Yao-Chou Tsai; Shi-Wen Kuo; Shiou-Chi Cherng; Ching-Chu Lu; Ruoh-Fang Yen; Vin-Cent Wu; Ya-Hui Hu Journal: Ci Ji Yi Xue Za Zhi Date: 2018 Jul-Sep