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Bradykinin Stimulates Renal Na+ and K+ Excretion by Inhibiting the K+ Channel (Kir4.1) in the Distal Convoluted Tubule.
Zhang, Dan-Dan; Gao, Zhong-Xiuzi; Vio, Carlos P; Xiao, Yu; Wu, Peng; Zhang, Hao; Guo, Xi-Wen; Meng, Xin-Xin; Gu, Li; Wang, Jun-Lin; Duan, Xin-Peng; Lin, Dao-Hong; Wang, Wen-Hui; Gu, Ruimin.
Afiliação
  • Zhang DD; From the Department of Physiology, Harbin Medical University, China (D.-D.Z., Y.X., H.Z., X.-W.G., X.-X.M., L.G., J.-L.W., X.-P.D., R.G.).
  • Gao ZX; Department of Pharmacology, New York Medical College, Valhalla (Z.-X.G., P.W., D.-H.L., W.-H.W.).
  • Vio CP; Department of Physiology, Center for Aging and Regeneration Care-UC, Pontificia Universidad Catolica de Chile, Santiago (C.P.V.).
  • Xiao Y; From the Department of Physiology, Harbin Medical University, China (D.-D.Z., Y.X., H.Z., X.-W.G., X.-X.M., L.G., J.-L.W., X.-P.D., R.G.).
  • Wu P; Department of Pharmacology, New York Medical College, Valhalla (Z.-X.G., P.W., D.-H.L., W.-H.W.).
  • Zhang H; From the Department of Physiology, Harbin Medical University, China (D.-D.Z., Y.X., H.Z., X.-W.G., X.-X.M., L.G., J.-L.W., X.-P.D., R.G.).
  • Guo XW; From the Department of Physiology, Harbin Medical University, China (D.-D.Z., Y.X., H.Z., X.-W.G., X.-X.M., L.G., J.-L.W., X.-P.D., R.G.).
  • Meng XX; From the Department of Physiology, Harbin Medical University, China (D.-D.Z., Y.X., H.Z., X.-W.G., X.-X.M., L.G., J.-L.W., X.-P.D., R.G.).
  • Gu L; From the Department of Physiology, Harbin Medical University, China (D.-D.Z., Y.X., H.Z., X.-W.G., X.-X.M., L.G., J.-L.W., X.-P.D., R.G.).
  • Wang JL; From the Department of Physiology, Harbin Medical University, China (D.-D.Z., Y.X., H.Z., X.-W.G., X.-X.M., L.G., J.-L.W., X.-P.D., R.G.).
  • Duan XP; From the Department of Physiology, Harbin Medical University, China (D.-D.Z., Y.X., H.Z., X.-W.G., X.-X.M., L.G., J.-L.W., X.-P.D., R.G.).
  • Lin DH; Department of Pharmacology, New York Medical College, Valhalla (Z.-X.G., P.W., D.-H.L., W.-H.W.).
  • Wang WH; Department of Pharmacology, New York Medical College, Valhalla (Z.-X.G., P.W., D.-H.L., W.-H.W.).
  • Gu R; From the Department of Physiology, Harbin Medical University, China (D.-D.Z., Y.X., H.Z., X.-W.G., X.-X.M., L.G., J.-L.W., X.-P.D., R.G.) ruimingu2916@163.com wenhui_wang@nymc.edu.
Hypertension ; 72(2): 361-369, 2018 08.
Article em En | MEDLINE | ID: mdl-29915013
ABSTRACT
Stimulation of BK2R (bradykinin [BK] B2 receptor) has been shown to increase renal Na+ excretion. The aim of the present study is to explore the role of BK2R in regulating Kir4.1 and NCC (NaCl cotransporter) in the distal convoluted tubule (DCT). Immunohistochemical studies demonstrated that BK2R was highly expressed in both apical and lateral membrane of Kir4.1-positive tubules, such as DCT. Patch-clamp experiments demonstrated that BK inhibited the basolateral 40-pS K+ channel (a Kir4.1/5.1 heterotetramer) in the DCT, and this effect was blocked by BK2R antagonist but not by BK1R (BK B1 receptor) antagonist. Whole-cell recordings also demonstrated that BK decreased the basolateral K+ conductance of the DCT and depolarized the membrane. Renal clearance experiments showed that BK increased urinary Na+ and K+ excretion. However, the BK-induced natriuretic effect was completely abolished in KS-Kir4.1 KO (kidney-specific conditional Kir4.1 knockout) mice, suggesting that Kir4.1 activity is required for BK-induced natriuresis. The continuous infusion of BK with osmotic pump for 3 days decreased the basolateral K+ conductance and the negativity of the DCT membrane. Western blot showed that infusion of BK decreased the expression of total NCC and phosphorylated NCC. Renal clearance experiments demonstrated that thiazide-induced natriuresis was blunted in the mice receiving BK infusion, suggesting that BK inhibited NCC function. Consequently, mice receiving BK infusion for 3 days were hypokalemic. We conclude that stimulation of BK2R inhibits NCC activity, increases urinary K+ excretion, and causes mice hypokalemia and that Kir4.1 is required for BK2R-mediated stimulation of urinary Na+ and K+ excretion.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Sódio / Bradicinina / Canais de Potássio Corretores do Fluxo de Internalização / Membro 3 da Família 12 de Carreador de Soluto / Túbulos Renais Distais / Natriurese Limite: Animals Idioma: En Revista: Hypertension Ano de publicação: 2018 Tipo de documento: Article
Texto completo
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Sódio / Bradicinina / Canais de Potássio Corretores do Fluxo de Internalização / Membro 3 da Família 12 de Carreador de Soluto / Túbulos Renais Distais / Natriurese Limite: Animals Idioma: En Revista: Hypertension Ano de publicação: 2018 Tipo de documento: Article