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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 Ca2+channel-induced Ca2+ 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.