Hypertension. 2014 Aug;64(2):397-404. doi: 10.1161/HYPERTENSIONAHA.114.03105. Epub 2014 Jun 2.

Transient receptor potential vanilloid 1 activation by dietary capsaicin promotes urinary sodium excretion by inhibiting epithelial sodium channel alpha subunit-mediated sodium reabsorption.External 2231691f894ba696de1310221b0a0dbbb31a7251e75115c265587c3d9d5f507c

Li, L., Wang, F., Wei, X., Liang, Y., Cui, Y., Gao, F., Zhong, J., Pu, Y., Zhao, Y., Yan, Z., Arendshorst, W. J., Nilius, B., Chen, J., Liu, D., Zhu, Z.,
["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.).", "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.).", "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.).", "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.).", "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.).", "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.).", "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.).", "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.).", "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.).", "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.).", "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.).", "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.).", "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.).", "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.).", "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."]
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 alphaENaC 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 alphaENaC activity in WT mice attributed to the HS diet. In contrast, this capsaicin effect was absent in TRPV1(-/-) mice. Immunoprecipitation study indicated alphaENaC 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 alphaENaC-mediated urinary sodium reabsorption. Dietary capsaicin may represent a promising lifestyle intervention in populations exposed to a high dietary salt intake.
PMID: 24890824External 2231691f894ba696de1310221b0a0dbbb31a7251e75115c265587c3d9d5f507c
Screening Toggle 893349bafcc528f8346c51dc3420151d67b0126b2c122dd1017121c03fa0f69b
  Experimental screening Non-experimental screening Reference
TRP channel construct Interactor source
TRP channel Interactor Method Species Region Species Organ/tissue Sample type
TRPV1 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 ơENaC Inference Prediction 24890824
(Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4: click the arrow icon to show interactions only between the corresponding TRP channel and the interactor)
Validation: In vivo validation Toggle 893349bafcc528f8346c51dc3420151d67b0126b2c122dd1017121c03fa0f69b
  Assay with endogenous proteins Assay with overexpressed proteins Reference
Cell or tissue Cell or tissue TRP channel construct Interactor construct
TRP channel Interactor Method Species Region Species Region
TRPV1 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 ơENaC Co-immunoprecipitation Mouse M1-cortical collecting duct 24890824
TRPV1 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 ơENaC Co-immunofluorescence staining Mouse M1-cortical collecting duct 24890824
(Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4: click the arrow icon to show interactions only between the corresponding TRP channel and the interactor)
TRP / Interactor

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