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

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

作者机构：Department of Hypertension and EndocrinologyCenter for Hypertension and Metabolic DiseasesDaping HospitalThird Military Medical UniversityChongqing Institute of HypertensionChongqing 400042China 

出 版 物：《Science China(Life Sciences)》 (中国科学（生命科学英文版）)

年 卷 期：2020年第63卷第11期

页      面：1665-1677页

核心收录：

学科分类：1002[医学-临床医学] 100201[医学-内科学(含：心血管病、血液病、呼吸系病、消化系病、内分泌与代谢病、肾病、风湿病、传染病)] 10[医学] 

基　　金：supported by grants from the National Natural Science Foundation of China (81721001, 81630015, 31701023) National Key Research and Development Project (2018YFA0800601) 

主　　题：transient receptor potential channel M5 bitter melon extract cardiovascular dysfunction 

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.