Angiotensin II and hypertonicity modulate proximal tubular aquaporin 1 expression.

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.

Duke Scholars

Author Shenglan Tang Population Health Sciences