Angiotensin II and hypertonicity modulate proximal tubular aquaporin 1 expression

Bouley R, Palomino Z, Tang S-S, Nunes P, Kobori H, Lu HA, Shum WW, Sabolic I, Brown D, Ingelfinger JR, Jung FF. Angiotensin II and hypertonicity modulate proximal tubular aquaporin 1 expression. Am J Physiol Renal Physiol 297: F1575-F1586, 2009. First published September 23, 2009; doi:10.1152/ajprenal.90762.2008.-Aquaporin 1 (AQP1) is the major water channel in the renal proximal tubule (PT) and thin descending limb of Henle, but its regulation remains elusive. Here, we investigated the effect of ANG II, a key mediator of body water homeostasis, on AQP1 expression in immortalized rat proximal tubule cells (IRPTC) and rat kidney. Real-time PCR on IRPTC exposed to ANG II for 12 h revealed a biphasic effect AQP1 mRNA increased dose dependently in response to 10(-12) to 10(-8) M ANG II but decreased by 50% with 10(-7) M ANG II. the twofold increase of AQP1 mRNA in the presence of 10(-8) M ANG II was abolished by the AT(1) receptor blocker losartan. Hypertonicity due to either NaCl or mannitol also upregulated AQP1 mRNA by three- and twofold, respectively. Immunocytochemistry and Western blotting revealed a two- to threefold increase in AQP1 protein expression in IRPTC exposed concomitantly to ANG II (10(-8)M) and hypertonic medium (either NaCl or mannitol), indicating that these stimuli were not additive. Three-dimensional reconstruction of confocal images suggested that AQP1 expression was increased by ANG II in both the apical and basolateral poles of IRPTC. in vivo studies showed that short-term ANG II infusion had a diuretic effect, while this effect was attenuated after several days of ANG II infusion. After 10 days, we observed a twofold increase in AQP1 expression in the PT and thin descending limb of Henle of ANG II-infused rats that was abolished when rats were treated with the selective AT(1)-receptor antagonist olmesartan. Thus ANG II increases AQP1 expression in vitro and in vivo via direct interaction with the AT(1) receptor, providing an important regulatory mechanism to link PT water reabsorption to body fluid homeostasis via the renin-angiotensin system.National Heart, Lung, and Blood InstituteNational Institute of Diabetes and Digestive and Kidney DiseasesNational Kidney Foundation Investigator AwardNational Sciences and Engineering Research CouncilBoston Area Diabetes and Endocrinology Research CenterCenter for the Study of Inflammatory Bowel DiseaseHarvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Syst Biol,Program Membrane Biol,Nephrol Div, Boston, MA 02114 USAUniversidade Federal de São Paulo, Escola Paulista Med, Disciplina Nephrol, São Paulo, BrazilHarvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA 02114 USATulane Univ, Hlth Sci Ctr, Dept Physiol & Hypertens, New Orleans, LA 70118 USAInst Med Res & Occupat Hlth, Zagreb 41000, CroatiaMassachusetts Gen Hosp, Boston, MA 02114 USAGeorgetown Univ, Dept Pediat, Washington, DC 20057 USAUniversidade Federal de São Paulo, Escola Paulista Med, Disciplina Nephrol, São Paulo, BrazilNational Heart, Lung, and Blood Institute: HL-40210National Heart, Lung, and Blood Institute: HL-48455National Institute of Diabetes and Digestive and Kidney Diseases: PO1-DK-38452National Institute of Diabetes and Digestive and Kidney Diseases: DK-38452Boston Area Diabetes and Endocrinology Research Center: DK-57521Center for the Study of Inflammatory Bowel Disease: DK-43351Web of Scienc