NaHCO 3 Dilates Mouse Afferent Arteriole Via Na + /HCO 3 − Cotransporters NBCs

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 NaHCO 3 dilates afferent arterioles (Af-Art) by stimulating nitric oxide (NO) release mediated by the Na + /HCO 3 − 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 3 (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 3 , 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 P 3 increased NO generation in Af-Art by 19±4% (n=5; P P 3 -induced increases in NO generation and vasodilation. We conclude that NBCn1 and NBCe1 are expressed in Af-Art and that NaHCO 3 dilates Af-Art via NBCs mediated by NO that increases the glomerular filtration rate.