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

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.

• Authors: Chia-Hung Chou, Ying-Hsien Chen, Chi-Sheng Hung, Yi-Yao Chang, Yu-Lin Tzeng, Xue-Ming Wu, Vin-Cent Wu, Chia-Ti Tsai, Cho-Kai Wu, Yi-Lwun Ho, Kwan-Dun Wu, Yen-Hung Lin, TAIPAI Study Group
• Journal: The Journal of clinical endocrinology and metabolism (J Clin Endocrinol Metab) Vol. 100 Issue 11 Pg. 4339-47 (Nov 2015) ISSN: 1945-7197 [Electronic] United States
• PMID: 26401591 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Nitrates
• RNA, Messenger
• Receptors, Mineralocorticoid
• Aldosterone
• Sarcoplasmic Reticulum Calcium-Transporting ATPases

Topics

• Adrenalectomy
• Adult
• Aldosterone (pharmacology)
• Blood Pressure
• Cells, Cultured
• Female
• Humans
• Hyperaldosteronism (metabolism, physiopathology, surgery)
• Male
• Middle Aged
• Muscle, Smooth, Vascular (cytology, drug effects)
• Nitrates (pharmacology)
• Prospective Studies
• RNA Interference
• RNA, Messenger (biosynthesis)
• Receptors, Mineralocorticoid (drug effects, metabolism)
• Sarcoplasmic Reticulum Calcium-Transporting ATPases (metabolism)
• Treatment Outcome
• Vasodilation (drug effects)