NaHCO3 Dilates mouse afferent arteriole via Na+/HCO3- cotransporters NBCs

Research output: Contribution to journalArticle

Authors

  • Shan Jiang
  • Ximing Wang
  • Jin Wei
  • Gensheng Zhang
  • Jie Zhang
  • Peng Xie
  • Lan Xu
  • Lei Wang
  • Liang Zhao
  • Lingli Li
  • Christopher S. Wilcox
  • Jianghua Chen
  • En Yin Lai
  • Ruisheng Liu

External Institution(s)

  • Zhejiang University
  • University of South Florida
  • Shandong University
  • Guangzhou Medical College
  • Charité – Universitätsmedizin Berlin
  • Georgetown University

Details

Original languageEnglish (US)
Pages (from-to)1104-1112
Number of pages9
JournalHypertension
Volume74
Issue number5
StatusPublished - Nov 1 2019
Peer-reviewedYes

Abstract

Sodium bicarbonate has long been used to treat chronic kidney disease. It has been demonstrated to slow the decline in glomerular filtration rate in chronic kidney disease patient; however, the mechanisms are not completely understood. We hypothesized that NaHCO3 dilates afferent arterioles (Af-Art) by stimulating nitric oxide (NO) release mediated by the Na+/HCO3- cotransporter (NBC) contributing to the elevation in glomerular filtration rate. Isolated microperfused mouse renal Af-Art, preconstricted with norepinephrine (1 μmol/L), dilated 45±2% (n=6, P<0.05) in response to NaHCO3 (44 mmol/L). Whereas, NaCl solution containing the same Na+ concentration was not effective. The mRNA for NBCn1 and NBCe1 were detected in microdissected Af-Art using reverse transcription-polymerase chain reaction and quantitative polymerase chain reaction. The Af-Art intracellular pH measured with 2′,7′-bis-(2-carboxyethyl)-5-(and-6) carboxyfluorescein, acetoxymethyl ester increased significantly by 0.29±0.02 (n=6; P<0.05) in the presence of NaHCO3, which was blunted by N-cyanosulphonamide compound (S0859) that is an inhibitor of the NBC family. After clamping the intracellular pH with 10 μM nigericin, changing the bath solution pH from 7.4 to 7.8 still dilates the Af-Art by 53±4% (n=7; P<0.005) and increases NO generation by 22±3% (n=7; P<0.005). Both pH-induced NO generation and vasodilation were blocked by L-NG-Nitroarginine Methyl Ester. NaHCO3 increased NO generation in Af-Art by 19±4% (n=5; P<0.005) and elevated glomerular filtration rate in conscious mice by 36% (233 versus 318 ul/min; n=9-10; P<0.0001). S0859 and L-NG-nitroarginine methyl ester blocked NaHCO3-induced increases in NO generation and vasodilation. We conclude that NBCn1 and NBCe1 are expressed in Af-Art and that NaHCO3 dilates Af-Art via NBCs mediated by NO that increases the glomerular filtration rate.

    Research areas

  • Arterioles, Glomerular filtration rate, Nitric oxide, Sodium bicarbonate, Vasodilation

Citation formats

APA

Jiang, S., Wang, X., Wei, J., Zhang, G., Zhang, J., Xie, P., ... Liu, R. (2019). NaHCO3 Dilates mouse afferent arteriole via Na+/HCO3- cotransporters NBCs. Hypertension, 74(5), 1104-1112. https://doi.org/10.1161/HYPERTENSIONAHA.119.13235

Harvard

Jiang, S, Wang, X, Wei, J, Zhang, G, Zhang, J, Xie, P, Xu, L, Wang, L, Zhao, L, Li, L, Wilcox, CS, Chen, J, Lai, EY & Liu, R 2019, 'NaHCO3 Dilates mouse afferent arteriole via Na+/HCO3- cotransporters NBCs', Hypertension, vol. 74, no. 5, pp. 1104-1112. https://doi.org/10.1161/HYPERTENSIONAHA.119.13235