Aldosterone Impairs Vascular Smooth Muscle Function: From Clinical to Bench Research

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 downregulation of mineralocorticoid receptor dependent mitochondrial transcription factors A and B2. Conclusions: Aldosterone impairs vascular smooth muscle cell function and suppresses SERCA 2a expression.