Department of Hypertension and Endocrinology, Daping Hospital, Third Military Medical University, Chongqing 400042, China.
Stroke. 2011 Nov;42(11):3245-51. doi: 10.1161/STROKEAHA.111.618306. Epub 2011 Aug 18.
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.
先前的研究表明，内皮型一氧化氮合酶（eNOS）在维持脑血流和预防中风方面起着重要作用。辣椒中的辣椒素可以增加内皮细胞中 eNOS 的磷酸化。我们通过测试以下假说来验证：通过激活易损性自发性高血压大鼠（SHRSP）脑血管瞬时受体电位香草酸 1 型（TRPV1）通道，慢性饮食辣椒素可以预防中风。
SHRSP 给予饮食辣椒素，并检查其中风发作情况。使用 TRPV1 敲除和转基因小鼠确定 TRPV1 通道的功能。检测 eNOS 的表达和脑血管反应性。
免疫荧光显示 TRPV1 通道和 eNOS 在脑小动脉中共同表达。辣椒素处理显著增加了野生型小鼠颈动脉中磷酸化 eNOS 的表达，但在 TRPV1 敲除小鼠中则没有。使用 N(G)-硝基-L-精氨酸甲酯抑制 eNOS、去除内皮或突变 TRPV1 显著降低了小鼠基底动脉中由辣椒素诱导的内皮依赖性舒张。慢性饮食辣椒素也显著增加了 SHRsp 颈动脉中 eNOS 的表达。与 Wistar-Kyoto 大鼠相比，SHRSP 基底动脉的内皮依赖性舒张明显受损。给予辣椒素或 L-精氨酸可显著改善 SHRsp 基底动脉的内皮依赖性舒张。SHRSP 脑小动脉肥大，饮食辣椒素可逆转这一现象。重要的是，长期给予辣椒素可显著延迟 SHRsp 中风的发作并延长其生存时间。
饮食辣椒素激活 TRPV1 通道介导 eNOS 磷酸化增加，可能成为饮食干预中风的新靶点。
