Morin ameliorates coronary artery relaxation by activating TRPV4-eNOS-NO signalling in high-salt diet-fed rats

Morin has been shown to be beneficial for Cardiovascular Disease. A high-salt diet induces dysfunction of coronary artery endothelial cells (CAECs), leading to altered regulation of coronary artery tone and increasing the risk of coronary artery diseases. In the present study, the protective effect of morin on the coronary artery was investigated in high-salt diet-induced hypertensive rats. Initially, morin pre-treatment of isolated rat coronary artery depressed the contraction induced by U46619, and morin induced endothelium-dependent relaxation of isolated rat coronary artery in a concentration-dependent manner. Moreover, the TRPV4 inhibitor HC067047, the nitric oxide (NO) synthase (eNOS) inhibitor L-NAME and a CA²⁺-free solution significantly reduced morin-induced coronary artery vasodilation. In primary CAECs, morin induced NO production; however, NO production was significantly reduced by HC067047 and L-NAME pre-treatment. Furthermore, the dose-dependent attenuating effect of morin was tested at doses of 50 and 100 mg/kg/day in high-salt diet-fed rats, and morin decreased blood pressure and significantly improved the relaxation response of the coronary arteries. Morin administration increased NO production in the coronary artery of high-salt diet-fed rats by activating TRPV4-eNOS signalling. In addition, oxidative stress levels were diminished by morin treatment in high-salt diet-fed rats. Western blot analyses confirmed that morin downregulated NOX2 expression. Thus, we demonstrate that morin induces endothelium-dependent relaxation in the rat coronary artery by activating TRPV4-eNOS-NO signalling, attenuates blood pressure, improves coronary artery vasodilation, and reduces coronary artery oxidative stress levels in individuals with high-salt diet-induced hypertension, highlighting the beneficial effect of morin in high-salt-induced coronary artery disease.

Coronary artery; Endothelial cell; High-salt diet; Morin; NO; TRPV4.