Activation of the bitter taste sensor TRPM5 prevents high salt-induced cardiovascular dysfunction
Activation of the bitter taste sensor TRPM5 prevents high salt-induced cardiovascular dysfunction
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苦味传感器TRPM5的激活可预防高盐引起的心血管功能障碍
DOI：
10.1007/s11427-019-1649-9
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发表时间：
2020
期刊：
影响因子：
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通讯作者：
Zhu Zhiming
中科院分区：
文献类型：
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作者：
Wu Hao;Cui Yuanting;He Chengkang;Gao Peng;Li Qiang;Zhang Hexuan;Jiang Yanli;Hu Yingru;Wei Xiao;Lu Zongshi;Ma Tianyi;Liu Daoyan;Zhu Zhiming
高盐摄入量是心血管疾病的已知危险因素。我们最近的研究表明，长期高盐摄入损害了瞬时受体电位通道M5(Trpm5)介导的对高盐浓度的厌恶，从而促进了高盐摄入和高血压；然而，激活Trpm5是否可以改善心血管功能障碍仍不清楚。在此，我们发现苦瓜提取物(BME)和苦瓜提取物中的主要化合物葫芦素E(CUE)能降低高盐诱导的高血压。长期摄入BME通过上调Trpm5的表达和功能，最终减少小鼠的过量食盐消耗，显著增强了小鼠对高盐浓度的厌恶。机制证据表明，饮食牛血清白蛋白抑制高盐诱导的RhoA/Rho激酶通路的过度激活，导致针对亚基1的肌球蛋白轻链激酶和肌球蛋白磷酸酶的磷酸化水平降低。此外，CUE通过抑制L型钙通道诱导的血管平滑肌细胞内钙内流而抑制血管收缩。综上所述，我们的研究结果表明，饮食中的BME在对抗过量盐摄入方面具有有益的作用，因此在预防高盐引起的心血管功能障碍方面似乎是有前途的。
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 hypertensionin 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.