Activation of the bitter taste sensor TRPM5 prevents high salt-induced cardiovascular dysfunction
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tivation of the bitter taste sensor TRPM5 prevents high saltinduced cardiovascular dysfunction †
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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 Department of Hypertension and Endocrinology, Center for Hypertension and Metabolic Diseases, Daping Hospital, Third Military Medical University, Chongqing Institute of Hypertension, Chongqing 400042, China Received December 10, 2019; accepted February 17, 2020; published online April 14, 2020
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 2+ 2+ inhibited vasoconstriction by attenuating L-type Ca channel-induced Ca 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. transient receptor potential channel M5, bitter melon extract, cardiovascular dysfunction Citation:
Wu, H., Cui, Y., He, C., Gao, P., Li, Q., Zhang, H., Jiang, Y., Hu, Y., Wei, X., Lu, Z., et al. (2020). Activation of the bitter taste sensor TRPM5 prevents high salt-induced cardiovascular dysfunction. Sci China Life Sci 63, https://doi.org/10.1007/s11427-019-1649-9
INTRODUCTION High salt intake is a well-known risk factor of hypertension and cardiovascular diseases. Reducing salt intake can significantly lower blood pressure and ameliorate target organ damage caused by hypertension (Bibbins-Domingo et al., 2010). However, in the past three decades, several strategies have failed to decrease daily salt intake to an optimal level (Powles et al., 2013). Therefore, it is important to identify alternative approaches for reducing excessive salt intake and antagonizing high salt-induced hypertension. †Contributed equally to this work *Corresponding author (email: [email protected])
Salt taste perception is an important factor in determining salt intake at an individual level. Previo
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