TRPV1 activation prevents high-salt diet-induced nocturnal hypertension in mice

Abstract

High dietary salt-caused hypertension is associated with increasing reactive oxygen species generation and reduced nitric oxide (NO) bioavailability. Transient receptor potential vanilloid type 1 (TRPV1), a specific receptor for capsaicin, is proposed to be involved in Dahl salt-sensitive hypertension, as determined in acute or short-term experiments. However, it remains unknown whether activation of TRPV1 by dietary capsaicin could prevent the vascular oxidative stress and hypertension induced by a high-salt diet. Here, we report that consumption of a high-salt diet blunted endothelium-dependent relaxation in mesenteric resistance arteries and elevated nocturnal blood pressure in mice. These effects were associated with increased superoxide anion generation and reduced NO levels in mesenteric vessels in mice on a high-salt diet. However, chronic administration of capsaicin reduced the high-salt diet-induced endothelial dysfunction and nocturnal hypertension in part by preventing the generation of superoxide anions and NO reduction of mesenteric arteries through vascular TRPV1 activation. Our findings provide new insights into the role of TRPV1 channels in the long-term regulation of blood pressure in response to high-salt intake. TRPV1 activation through chronic dietary capsaicin may represent a promising lifestyle intervention in populations with salt-sensitive hypertension.

Transient Receptor Potential Vanilloid 1 Activation by Dietary Capsaicin Promotes Urinary Sodium Excretion by Inhibiting Epithelial Sodium Channel α Subunit–Mediated Sodium Reabsorption

“…8 Chronic administration of capsaicin reduced the HS diet-induced endothelial dysfunction and nocturnal hypertension in part by preventing the generation of superoxide anions and NO reduction in mesenteric arteries in WT mice. 25 Several studies show the benefits of chili pepper in human. Long-term consumption of a diet high in chilies has been shown to improve arterial function in human.…”

Transient Receptor Potential Channels as Drug Targets: From the Science of Basic Research to the Art of Medicine

“…Capsaicin was reported to constrict smooth muscle cells isolated from the rat gracilis arterioles via TRPV1 (Kark et al, 2008). The significance of this finding is unclear since TRPV1 knockout animals have no relevant phenotype and capsaicin actually prevents the development of hypertension in rats kept on a high-salt diet (Hao et al, 2011). Dietary capsaicin also delays the onset of stroke in spontaneously hypertensive rats .…”

Update on vascular endothelial Ca2+signalling: A tale of ion channels, pumps and transporters

“….-anions and NO reduction through vascular TRPV1 activation [281] . Baseline mean arterial pressures are, however, not statistically different in wild-type and TRPV1 -/-mice [282,283] .…”