Activation of Transient Receptor Potential Vanilloid 1 by Dietary Capsaicin Delays the Onset of Stroke in Stroke-Prone Spontaneously Hypertensive Rats

Previous studies show that endothelial nitric oxide synthase (eNOS) plays a prominent role in maintaining cerebral blood flow and preventing stroke. Capsaicin in hot pepper can increase the phosphorylation of eNOS in endothelial cells. We test the hypothesis that chronic dietary capsaicin can prevent stroke through activation of cerebrovascular transient receptor potential vanilloid 1 (TRPV1) channels in stroke-prone spontaneously hypertensive rats (SHRsp). SHRsp were fed dietary capsaicin, and their onset of stroke was examined. TRPV1 knockout and transgenic mice were used for determining the function of TRPV1 channels. Expression of eNOS and cerebrovascular reactivity were examined. Immunofluorescence showed TRPV1 channels and eNOS coexpression in cerebral arterioles. Administration of capsaicin significantly increased phosphorylated eNOS in carotid arteries from wild-type mice but not in TRPV1 knockout mice. Inhibition of eNOS using N(G)-nitro-L-arginine methyl ester, removal of endothelium, or mutant TRPV1 significantly reduced capsaicin-induced endothelium-dependent relaxation of basilar arteries in mice. Chronic dietary capsaicin also remarkably increased eNOS expression in carotid arteries from SHRsp. Compared with Wistar-Kyoto rats, SHRsp had impaired endothelium-dependent relaxation of basilar arteries. Administration of capsaicin or L-arginine significantly improved the endothelium-dependent relaxation of basilar arteries in SHRsp. SHRsp had hypertrophy of cerebral arterioles, which was reversed by dietary capsaicin. Importantly, long-term administration of capsaicin significantly delayed the onset of stroke and increased the survival time in SHRsp. Activation of TRPV1 channels by dietary capsaicin mediated increases in phosphorylation of eNOS and could represent a novel target for dietary intervention of stroke.