Overexpression of ANO1/TMEM16A, an arterial Ca2+-activated Cl- channel, contributes to spontaneous hypertension.

Abstract

Calcium-activated chloride channels (CaCCs) have been implicated in hypertension; however, the mechanism underlying their involvement is unknown. The aim of this study was to determine whether the CaCC ANO1 is involved in the pathogenesis of spontaneous hypertension. Arterial ANO1 expression and the effects on blood pressure (BP) of inhibiting ANO1 with an ANO1 inhibitor, T16(Ainh)-A01, and in vivo RNAi, were examined in spontaneously hypertensive rats (SHRs). Knockdown of ANO1 by siRNA prevented hypertensive development, and attenuation of ANO1 channel activity reduced BP in SHRs. Angiotensin II upregulated ANO1 expression in primary cultures of vascular smooth muscle cells (VSMCs). The protein level and activity of cellular ANO1 positively correlated with VSMC proliferation. Our data indicate an important role of increased ANO1 expression and activity in inducing hypertension in SHRs. It may mediate angiotensin II-dependent vascular remodeling. Our results increase the mechanistic understanding of hypertension and suggest ANO1 as a possible therapeutic target for hypertension.

• Authors: Bingxiang Wang, Chunlin Li, Ruituo Huai, Zhiqiang Qu
• Journal: Journal of molecular and cellular cardiology (J Mol Cell Cardiol) Vol. 82 Pg. 22-32 (May 2015) ISSN: 1095-8584 [Electronic] England
• PMID: 25739000 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015. Published by Elsevier Ltd.

Chemical References

• ANO1 protein, rat
• Anoctamin-1
• Chloride Channels
• Receptor, Angiotensin, Type 1
• Angiotensin II

Topics

• Angiotensin II (pharmacology)
• Animals
• Anoctamin-1
• Arteries (drug effects, metabolism)
• Blood Pressure (drug effects)
• Cell Proliferation
• Chloride Channels (antagonists & inhibitors, genetics, metabolism)
• Disease Models, Animal
• Excitation Contraction Coupling (drug effects)
• Gene Expression
• Gene Knockdown Techniques
• Glycosylation
• Male
• Models, Biological
• Muscle, Smooth, Vascular (drug effects, metabolism)
• Myocytes, Smooth Muscle (drug effects, metabolism)
• Rats
• Rats, Inbred SHR (genetics, metabolism)
• Receptor, Angiotensin, Type 1 (metabolism)
• Signal Transduction (drug effects)