Activation of TRPV1 by Dietary Capsaicin Improves Endothelium-Dependent Vasorelaxation and Prevents Hypertension

Abstract

SUMMARY Some plant-based diets lower the cardiometabolic risks and prevalence of hypertension. New evidence implies a role for the transient receptor potential vanilloid 1 (TRPV1) cation channel in the pathogenesis of cardiometabolic diseases. Little is known about impact of chronic TRPV1 activation on the regulation of vascular function and blood pressure. Here we report that chronic TRPV1 activation by dietary capsaicin increases the phosphorylation of protein kinase A (PKA) and eNOS and thus production of nitric oxide (NO) in endothelial cells, which is calcium dependent. TRPV1 activation by capsaicin enhances endothelium-dependent relaxation in wild-type mice, an effect absent in TRPV1-deficient mice. Long-term stimulation of TRPV1 can activate PKA, which contributes to increased eNOS phosphorylation, improves vasorelaxation, and lowers blood pressure in genetically hypertensive rats. We conclude that TRPV1 activation by dietary capsaicin improves endothelial function. TRPV1-mediated increase in NO production may represent a promising target for therapeutic intervention of hypertension.

Asymmetric Dimethylarginine Limits the Efficacy of Simvastatin Activating Endothelial Nitric Oxide Synthase

“…Activation of eNOS‐NO signaling is suggested to be a major mechanism of clinical therapeutic drugs in treating cardiovascular diseases 26, 27, 28. eNOS can be activated by physiological and metabolic stimuli, such as shear stress and clinical therapeutic drugs, and result in NO production.…”

Imbalance and dysfunction of transient receptor potential channels contribute to the pathogenesis of hypertension

“…In vivo, plasma concentration of CGRP rises transiently after acute administration of capsaicin in adult rats, accompanied by a decrease in blood pressure [71]. In a previous study, we showed that the TRPV1 agonist capsaicin acutely relaxed mesenteric arteries through at least two mechanisms: a direct action on ECs, which was NO dependent and L-NAME sensitive, and the release of CGRP, which activated an L-NAME-insensitive pathway, but to a lesser degree [26]. Activation of TRPV1 enhanced endothelium-dependent relaxation in wild-type mice, an effect absent in TRPV1-deficient mice [26].…”

“…Growing evidence suggests that TRPV1 channels play multiple important roles in hypertension via several different mechanisms. TRPV1 activation exerts antihypertension effects by stimulating the release of calcitonin gene-related peptide (CGRP) from capsaicin-sensitive sensory nerves and NO from ECs [26,70]. In vivo, plasma concentration of CGRP rises transiently after acute administration of capsaicin in adult rats, accompanied by a decrease in blood pressure [71].…”

“…TRPV1 is abundant in the endothelium. In freshly isolated rodent mesenteric arteries, activation of TPRV1 by its agonist capsaicin elicited an acute release of NO from ECs and vasodilatation, which was inhibited by the TRPV1 antagonists and was absent from arteries of TRPV1-deficient mice [26]. TRPV4 channels in the vascular ECs and SMCs are critically involved in the vasodilatation of mesenteric arteries in response to endothelial-derived factors [28].…”

“…In a previous study, we showed that the TRPV1 agonist capsaicin acutely relaxed mesenteric arteries through at least two mechanisms: a direct action on ECs, which was NO dependent and L-NAME sensitive, and the release of CGRP, which activated an L-NAME-insensitive pathway, but to a lesser degree [26]. Activation of TRPV1 enhanced endothelium-dependent relaxation in wild-type mice, an effect absent in TRPV1-deficient mice [26]. In another study, long-term stimulation of TRPV1 by dietary capsaicin attenuated hypertension in SHRs [26].…”