Activation of the bitter taste sensor TRPM5 prevents high saltinduced cardiovascular dysfunction

查看全文 作　　者：Hao [1]Wu;Yuanting [1]Cui;Chengkang [1]He;Peng [1]Gao;Qiang [1]Li;Hexuan [1]Zhang;Yanli [1]Jiang;Yingru [1]Hu;Xiao [1]Wei;Zongshi [1]Lu;Tianyi [1]Ma;Daoyan [1]Liu;Zhiming [1]Zhu

机构地区：[1]Department of Hypertension and Endocrinology,Center for Hypertension and Metabolic Diseases,Daping Hospital,Third Military Medical University,Chongqing Institute of Hypertension,Chongqing 400042,China

出　　处：《Science China(Life Sciences)》索引2020年第63卷第11期,共13页

基　　金：supported by grants from the National Natural Science Foundation of China (81721001, 81630015, 31701023);National Key Research and Development Project (2018YFA0800601)。 摘　　要：High salt intake is a known risk factor of cardiovascular diseases. Our recent study demonstrated that long-term high salt intake impairs transient receptor potential channel M5(TRPM5)-mediated aversion to high salt concentrations, consequently promoting high salt intake and hypertension;however, it remains unknown whether TRPM5 activation ameliorates cardiovascular dysfunction. Herein we found that bitter melon extract(BME) and cucurbitacin E(CuE), a major compound in BME, lowered high salt-induced hypertension. Long-term BME intake significantly enhanced the aversion to high salt concentrations by upregulating TRPM5 expression and function, eventually decreasing excessive salt consumption in mice. Moreover, dietary BME ameliorated high salt-induced cardiovascular dysfunction and angiotensin II-induced hypertension in vivo. The mechanistic evidence demonstrated that dietary BME inhibited high salt-induced RhoA/Rho kinase pathway overactivation, leading to reduced phosphorylation levels of myosin light chain kinase and myosin phosphatase targeting subunit 1. Furthermore, CuE inhibited vasoconstriction by attenuating L-type Ca^(2+) channel-induced Ca^(2+) influx in vascular smooth muscle cells. To summarize, our findings indicate that dietary BME has a beneficial role in antagonizing excessive salt consumption and thus appears promising for the prevention of high salt-induced cardiovascular dysfunction. 关键词：transient receptor potential channel M5 bitter melon extract cardiovascular dysfunction

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Activation of the bitter taste sensor TRPM5 prevents high saltinduced cardiovascular dysfunction

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