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

Abstract

Background and Purpose-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). Methods-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. Results-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. Conclusions-Activation

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

“…Several studies have shown that capsaicin and its target, TRPV1, are implicated in hypertension. 20 The renal sensory nerves that express TRPV1, and various neuropeptides, including potent vasodilators, are released on TRPV1 activation. 21 Rats develop salt-sensitive hypertension after TRPV1 sensory degeneration by capsaicin treatment.…”

Dietary Curcumin Ameliorates Aging-Related Cerebrovascular Dysfunction through the AMPK/Uncoupling Protein 2 Pathway

“…Some arteries were incubated with the nitric oxide synthase (NOS) inhibitor L-NAME (100 μmol/L, 30 minutes) before measuring EDR. Endothelium-independent relaxation in response to nitroglycerin (NTG) was measured in basilar rings [22,23]. …”

Pharmacological hypothermia: a potential for future stroke therapy?

“…The endogenous cannabinoid signaling system or endocannabinoid (eCB) system, which involves arachidonic Cannabinoid System (49)(50)(51)(52)(53) WIN55212-2 CB1 agonist at POAH (57,58) Reduced excitotoxicity via glutamate release (50) Titrated 1-10 mg/kg (50) Dose dependent: (50,52) Sprague-Dawley rats (52) 1 mg/kg 1 mg/kg  0 °C (53) Wistar rats (53) 9 mg/kg with active rewarming 2.5 mg/kg  -2.5 °C (59,60) Remyelination through oligodendrocyte proliferation 5 mg/kg  -3.4 °C 10 mg/kg  -3.4 °C (52) 1 mg/kg  0 °C (52) Reduced inflammation and microglia activation (61) Reduced BBB disruption (54) HU-210 (71)(72)(73) Capsaicin Effects through peripheral nerves and POAH (71) Phosphorylation of eNOS (72) ↓ Blood pressure (72) 0.02% standard chow (72) Stroke-prone spontaneously hypertensive rats (73) 0.3 mg/kg (73) Dogs (76) Anti-shivering thermoregulatory effects ↓ Heart rate (73) Transient ↓ blood pressure and ↓ Heart rate (75) Lead to neuronal apoptosis (74) DHC …”

“…74 Capsaicin (0.02% added to standard chow) has been shown to have protective effects against stroke via increased phosphorylation of endothelial nitric oxide synthase (eNOS) in stroke-prone spontaneously hypertensive rats. 75 However, studies have shown capsaicin (5-20 μg/kg) to have cardiovascular depressive effects such as hypotension and bradycardia in dogs. 76 A recent study has determined that the above effect may be due to impurities present in the administered capsaicin, as pure trans-capsaicin (0.3 mg/kg) only resulted in transient tachycardia and hypertension.…”