title: Transient receptor potential vanilloid 1 activation by dietary capsaicin promotes urinary sodium excretion by inhibiting epithelial sodium channel α subunit-mediated sodium reabsorption.
abstract: 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.
authors.affiliation: 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.).
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.affiliation: 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.).
authors.forename: Fei
authors.initials: F
authors.lastname: Wang
authors.affiliation: 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.).
authors.forename: Xing
authors.initials: X
authors.lastname: Wei
authors.affiliation: 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.).
authors.forename: Yi
authors.initials: Y
authors.lastname: Liang
authors.affiliation: 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.).
authors.forename: Yuanting
authors.initials: Y
authors.lastname: Cui
authors.affiliation: 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.).
authors.forename: Feng
authors.initials: F
authors.lastname: Gao
authors.affiliation: 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.).
authors.forename: Jian
authors.initials: J
authors.lastname: Zhong
authors.affiliation: 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.).
authors.forename: Yunfei
authors.initials: Y
authors.lastname: Pu
authors.affiliation: 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.).
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: 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.).
authors.forename: Zhencheng
authors.initials: Z
authors.lastname: Yan
authors.affiliation: 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.).
authors.forename: William J
authors.initials: WJ
authors.lastname: Arendshorst
authors.affiliation: 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.).
authors.forename: Bernd
authors.initials: B
authors.lastname: Nilius
authors.affiliation: 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.).
authors.forename: Jing
authors.initials: J
authors.lastname: Chen
authors.affiliation: 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.).
authors.forename: Daoyan
authors.initials: D
authors.lastname: Liu
authors.affiliation: 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.). zhuzm@yahoo.com daoyanliu@yahoo.com.
authors.forename: Zhiming
authors.initials: Z
authors.lastname: Zhu
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002211:Capsaicin / Q000008:administration & dosage*; D053503:Epithelial Sodium Channels / Q000378:metabolism*; D006973:Hypertension / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D012964:Sodium / Q000378:metabolism*; D050916:TRPV Cation Channels / Q000235:genetics / Q000378:metabolism*
chemical_list: D053503:Epithelial Sodium Channels; D050916:TRPV Cation Channels; C493921:TRPV1 protein, mouse; D012964:Sodium; D002211:Capsaicin
keywords: capsaicin ENaC alpha; hypertension kidney collecting duct sodium diet transient receptor potential cation channel V1