Regulation of glomerulotubular balance. II. Impact of angiotensin II on flow-dependent transport
Regulation of glomerulotubular balance. II. Impact of angiotensin II on flow-dependent transport
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DOI：
10.1152/ajprenal.00277.2012
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发表时间：
2012-12-01
影响因子：
4.2
通讯作者：
Wang, Tong
中科院分区：
文献类型：
--
作者：
Du, Zhaopeng;Wan, Laxiang;Wang, Tong
Du Z, Wan L, Yan Q, Weinbaum S, Weinstein AM, Wang T. Regulation of glomerulotubular balance. II. Impact of angiotensin II on flow-dependent transport. Am J Physiol Renal Physiol 303: F1507-F1516, 2012. First published September 5, 2012; doi:10.1152/ajprenal.00277.2012.-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 (J(v)) and HCO3- (J(HCO3)) absorption and cell height were measured. Na+ (J(Na)) and Cl- (J(Cl)) 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 AT(1a) knockout (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 JHCO3 was eliminated by the H-ATPase inhibitor bafilomycin. Inhibition of the AT(2) receptor by PD123319 increased both JNa and J(HCO3) but did not affect flowmediated fractional changes. NHE3 expression at the protein level was reduced in AT(1a) KO mice kidneys. We conclude that 1) although the AT1a receptor is necessary for flow to impact NHE3, the effect on H+-ATPase is independent of AT(1a); 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.
