Regulation of glomerulotubular balance. II. Impact of angiotensin II on flow-dependent transport

Abstract

Underlying glomerulotubular balance (GTB) is the impact of axial flow to regulate Na+and HCO3−transport by modulating Na+-H+exchanger 3 (NHE3) and H-ATPase activity. It is not known whether the cascade of events following a change in flow relies on local angiotensin (ANG II) generation or receptor availability. Mouse tubules were microperfused in vitro at flows of 5 and 20 nl/min, and net fluid (Jv) and HCO3−(JHCO3) absorption and cell height were measured. Na+(JNa) and Cl−(JCl) absorption and changes in microvillous torque were estimated. Raising flow increased Na+and HCO3−reabsorption but did not change either Cl−transport or cell volume. Losartan reduced absolute Na+and HCO3−absorption at both low and high flows but did not affect fractional flow-stimulated transport. Compared with controls, in AT1aknockout (KO) mouse tubules, 53% of flow-stimulated Na+absorption was abolished, but flow-stimulated HCO3−absorption was retained at similar levels. The remaining flow-stimulated JHCO3was eliminated by the H-ATPase inhibitor bafilomycin. Inhibition of the AT2receptor by PD123319 increased both JNaand JHCO3but did not affect flow-mediated fractional changes. NHE3 expression at the protein level was reduced in AT1aKO mice kidneys. We conclude that 1) although the AT1areceptor is necessary for flow to impact NHE3, the effect on H+-ATPase is independent of AT1a; 2) the small flow-mediated changes in cell volume suggest a coordinate flow effect on both luminal and basolateral transporters; and 3) there is no evidence of flow-dependent Cl−transport, and thus no evidence for convective paracellular Cl−transport in mouse tubules.