PMID- 22952281 OWN - NLM STAT- MEDLINE DCOM- 20130402 LR - 20211021 IS - 1522-1466 (Electronic) IS - 1931-857X (Print) IS - 1522-1466 (Linking) VI - 303 IP - 11 DP - 2012 Dec 1 TI - Regulation of glomerulotubular balance: II: impact of angiotensin II on flow-dependent transport. PG - F1507-16 LID - 10.1152/ajprenal.00277.2012 [doi] AB - Underlying glomerulotubular balance (GTB) is the impact of axial flow to regulate Na(+) and HCO(3)(-) 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 HCO(3)(-) (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 HCO(3)(-) reabsorption but did not change either Cl(-) transport or cell volume. Losartan reduced absolute Na(+) and HCO(3)(-) 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 HCO(3)(-) absorption was retained at similar levels. The remaining flow-stimulated J(HCO3) was eliminated by the H-ATPase inhibitor bafilomycin. Inhibition of the AT(2) receptor by PD123319 increased both J(Na) and J(HCO3) but did not affect flow-mediated fractional changes. NHE3 expression at the protein level was reduced in AT(1a) KO mice kidneys. We conclude that 1) although the AT(1a) 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. FAU - Du, Zhaopeng AU - Du Z AD - Dept. of Cellular and Molecular Physiology, Yale School of Medicine, New Haven, CT 06520-8026, USA. FAU - Wan, Laxiang AU - Wan L FAU - Yan, Qingshang AU - Yan Q FAU - Weinbaum, Sheldon AU - Weinbaum S FAU - Weinstein, Alan M AU - Weinstein AM FAU - Wang, Tong AU - Wang T LA - eng GR - R01 DK029857/DK/NIDDK NIH HHS/United States GR - R01-DK-29857/DK/NIDDK NIH HHS/United States GR - R01-DK62289/DK/NIDDK NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20120905 PL - United States TA - Am J Physiol Renal Physiol JT - American journal of physiology. Renal physiology JID - 100901990 RN - 0 (Angiotensin II Type 1 Receptor Blockers) RN - 0 (Bicarbonates) RN - 0 (Enzyme Inhibitors) RN - 0 (Macrolides) RN - 0 (Receptor, Angiotensin, Type 1) RN - 0 (Slc9a3 protein, mouse) RN - 0 (Sodium-Hydrogen Exchanger 3) RN - 0 (Sodium-Hydrogen Exchangers) RN - 11128-99-7 (Angiotensin II) RN - 116764-51-3 (bafilomycin A) RN - 9NEZ333N27 (Sodium) RN - EC 3.6.3.14 (Proton-Translocating ATPases) RN - JMS50MPO89 (Losartan) SB - IM MH - Angiotensin II/*physiology MH - Angiotensin II Type 1 Receptor Blockers/pharmacology MH - Animals MH - Bicarbonates/*metabolism MH - Biological Transport/physiology MH - Enzyme Inhibitors/pharmacology MH - Female MH - Hemostasis/drug effects/*physiology MH - In Vitro Techniques MH - Kidney Glomerulus/drug effects/*metabolism MH - Kidney Tubules/drug effects/*metabolism MH - Losartan/pharmacology MH - Macrolides/pharmacology MH - Mice MH - Mice, Knockout MH - Models, Animal MH - Proton-Translocating ATPases/antagonists & inhibitors/metabolism MH - Receptor, Angiotensin, Type 1/deficiency/genetics/metabolism MH - Sodium/*metabolism MH - Sodium-Hydrogen Exchanger 3 MH - Sodium-Hydrogen Exchangers/metabolism PMC - PMC3532483 EDAT- 2012/09/07 06:00 MHDA- 2013/04/03 06:00 PMCR- 2013/12/01 CRDT- 2012/09/07 06:00 PHST- 2012/09/07 06:00 [entrez] PHST- 2012/09/07 06:00 [pubmed] PHST- 2013/04/03 06:00 [medline] PHST- 2013/12/01 00:00 [pmc-release] AID - ajprenal.00277.2012 [pii] AID - F-00277-2012 [pii] AID - 10.1152/ajprenal.00277.2012 [doi] PST - ppublish SO - Am J Physiol Renal Physiol. 2012 Dec 1;303(11):F1507-16. doi: 10.1152/ajprenal.00277.2012. Epub 2012 Sep 5.