Overexpression of ANO1/TMEM16A, an arterial Ca2+-activated Cl- channel, contributes to spontaneous hypertension.
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.
Department of Physiology, Center for Medical Research, the First Affiliated Hospital, Medical College of Qingdao University, Qingdao 266071, China; Department of Physiology, Taishan Medical College, Taian 271000, China. Electronic address: wangbingxiang352@163.com.
Bingxiang
B
Wang
Department of Physiology, Center for Medical Research, the First Affiliated Hospital, Medical College of Qingdao University, Qingdao 266071, China. Electronic address: lys_cysteine@126.com.
Chunlin
C
Li
Robot Research Center, Shandong University of Science and Technology, Qingdao 266510, China. Electronic address: huairuituo@163.com.
Ruituo
R
Huai
Department of Physiology, Center for Medical Research, the First Affiliated Hospital, Medical College of Qingdao University, Qingdao 266071, China. Electronic address: 18661801173@163.com.
Zhiqiang
Z
Qu
D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D000075369:Anoctamin-1; D001158:Arteries / Q000187:drug effects / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D049109:Cell Proliferation; D018118:Chloride Channels / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D004195:Disease Models, Animal; D056966:Excitation Contraction Coupling / Q000187:drug effects; D015870:Gene Expression; D055785:Gene Knockdown Techniques; D006031:Glycosylation; D008297:Male; D008954:Models, Biological; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR / Q000235:genetics* / Q000378:metabolism; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
C552942:ANO1 protein, rat; D000075369:Anoctamin-1; D018118:Chloride Channels; D044140:Receptor, Angiotensin, Type 1; D000804:Angiotensin II
ANO1; Ca(2+)-activated Cl(−) channel; Hypertension; Spontaneously hypertensive rats