From the Department of Hypertension and Endocrinology, Center for Hypertension and Metabolic Diseases, Daping Hospital, Third Military Medical University, Chongqing Institute of Hypertension, Chongqing, China (L.L., F.W., X.W., Y.L., Y.C., F.G., J.Z., Y.P., Y.Z., Z.Y., J.C., D.L., Z.Z.); Department of Cell Biology and Physiology, School of Medicine, University of North Carolina at Chapel Hill (W.J.A.); and Department of Cell Molecular Medicine, Laboratory Ion Channel Research, Campus Gasthuisberg, Leuven, Belgium (B.N.).
Hypertension. 2014 Aug;64(2):397-404. doi: 10.1161/HYPERTENSIONAHA.114.03105. Epub 2014 Jun 2.
High salt (HS) intake contributes to the development of hypertension. Epithelial sodium channels play crucial roles in regulating renal sodium reabsorption and blood pressure. The renal transient receptor potential vanilloid 1 (TRPV1) cation channel can be activated by its agonist capsaicin. However, it is unknown whether dietary factors can act on urinary sodium excretion and renal epithelial sodium channel (ENaC) function. Here, we report that TRPV1 activation by dietary capsaicin increased urinary sodium excretion through reducing sodium reabsorption in wild-type (WT) mice on a HS diet but not in TRPV1(-/-) mice. The effect of capsaicin on urinary sodium excretion was involved in inhibiting αENaC and its related with-no-lysine kinase 1/serum- and glucocorticoid-inducible protein kinase 1 pathway in renal cortical collecting ducts of WT mice. Dietary capsaicin further reduced the increased αENaC activity in WT mice attributed to the HS diet. In contrast, this capsaicin effect was absent in TRPV1(-/-) mice. Immunoprecipitation study indicated αENaC specifically coexpressed and functionally interact with TRPV1 in renal cortical collecting ducts of WT mice. Additionally, ENaC activity and expression were suppressed by capsaicin-mediated TRPV1 activation in cultured M1-cortical collecting duct cells. Long-term dietary capsaicin prevented the development of high blood pressure in WT mice on a HS diet. It concludes that TRPV1 activation in the cortical collecting ducts by capsaicin increases urinary sodium excretion and avoids HS diet-induced hypertension through antagonizing αENaC-mediated urinary sodium reabsorption. Dietary capsaicin may represent a promising lifestyle intervention in populations exposed to a high dietary salt intake.
高盐（HS）摄入会导致高血压的发生。上皮钠通道在调节肾脏钠重吸收和血压方面起着至关重要的作用。瞬时受体电位香草醛 1 型（TRPV1）阳离子通道可以被其激动剂辣椒素激活。然而，尚不清楚饮食因素是否可以作用于尿钠排泄和肾脏上皮钠通道（ENaC）功能。在这里，我们报告饮食辣椒素通过减少 HS 饮食野生型（WT）小鼠肾脏皮质集合管中的钠重吸收来增加尿钠排泄，但在 TRPV1（-/-）小鼠中则没有。辣椒素对尿钠排泄的影响涉及抑制αENaC及其相关的无赖氨酸激酶 1/血清和糖皮质激素诱导蛋白激酶 1 途径在 WT 小鼠肾脏皮质集合管中的作用。饮食辣椒素进一步降低了 WT 小鼠因 HS 饮食而增加的αENaC 活性。相比之下，这种辣椒素的作用在 TRPV1（-/-）小鼠中不存在。免疫沉淀研究表明，αENaC 在 WT 小鼠的肾脏皮质集合管中特异性共表达并与 TRPV1 发生功能相互作用。此外，在培养的 M1-皮质集合管细胞中，辣椒素介导的 TRPV1 激活抑制了 ENaC 活性和表达。长期饮食辣椒素可预防 WT 小鼠因 HS 饮食而引起的高血压的发生。这表明，通过拮抗αENaC 介导的尿钠重吸收，辣椒素在皮质集合管中对 TRPV1 的激活增加了尿钠排泄，并避免了 HS 饮食引起的高血压。饮食辣椒素可能代表一种有前途的生活方式干预，适用于摄入高盐饮食的人群。
