[Activation of transient receptor potential vanilloid 1 inhibits RhoA/Rho kinase and improves vasorelaxation dysfunction mediated by high-fat diet in mice].

OBJECTIVE: To investigate the role of dietary capsaicin in activating transient receptor potential vanilloid 1 (TRPV1) and thus influencing the vascular dysfunction mediated by high-fat diet and the potential mechanisms.
METHODS: A total of 80 male C57BL/6J mice aged 10 weeks were equally divided into four groups, in which the mice were fed with normal diet (ND), normal diet plus capsaicin (NC), high-fat diet (HD), or high-fat diet plus capsaicin (HC) for 20 weeks. Tail-cuff blood pressure (BP), vascular function of mice aortic rings, expressions of voltage-gated potassium-channel Kv1.4, RhoA and Rho kinase in aorta were examined.
RESULTS: Compared with ND group, both nitroglycerin [(18.9 +/- 13)% vs. 100%, P < 0.01] and acetylcholine [(26 +/- 12)% vs. 100%, P < 0.01] induced vasorelaxation of aortic rings were significantly reduced in HD group. Both endothelium dependent and independent aortic rings vasorelaxation in HC group were significantly improved compared with that in HD group [acetylcholine: (69 +/- 15)%; nitroglycerin: (46.5 +/- 6)%, P < 0.05], but still reduced compared with that in ND group (P < 0.05, P < 0.01). High fat diet induced the expression of RhoA and Rho kinase. Dietary capsaicin down-regulated the expression of RhoA and Rho kinase but up-regulated the expression of Kv1.4 in aorta in mice fed with normal or high fat diet (all P < 0.05).
CONCLUSION: Dietary capsaicin can ameliorate vasorelaxation dysfunction mediated by high-fat diet. The potential mechanisms may be related with TRPV1 activation, which in turn stimulates potassium channel and inhibits RhoA and Rho kinase in the vasculature.