AT(1a) receptor signaling is required for basal and water deprivation-induced urine concentration in AT(1a) receptor-deficient mice

作者：Li Xiao C; Shao Yuan; Zhuo Jia L^*

来源：American Journal of Physiology - Renal Fluid and Electrolyte Physiology, 2012, 303(5): F746-F756.

DOI：10.1152/ajprenal.00644.2011

• angiotensin II
• angiotensin II type 1a receptor
• adenylyl cyclases
• aquaporin 2
• arginine vasopressin
• inner medullary collecting ducts
• urine concentration

Li XC, Shao Y, Zhuo JL. AT(1a) receptor signaling is required for basal and water deprivation-induced urine concentration in AT(1a) receptor-deficient mice. Am J Physiol Renal Physiol 303: F746-F756, 2012. First published June 27, 2012; doi: 10.1152/ajprenal.00644.2011.-It is well recognized that ANG II interacts with arginine vasopressin (AVP) to regulate water reabsorption and urine concentration in the kidney. The present study used ANG II type 1a (AT(1a)) receptor-deficient (Agtr1a(-/-)) mice to test the hypothesis that AT(1a) receptor signaling is required for basal and water deprivation-induced urine concentration in the renal medulla. Eight groups of wild-type (WT) and Agtr1a(-/-) mice were treated with or without 24-h water deprivation and 1-desamino-8-D-AVP (DDAVP; 100 ng/h ip) for 2 wk or with losartan (10 mg/kg ip) during water deprivation. Under basal conditions, Agtr1a(-/-) mice had lower systolic blood pressure (P %26lt; 0.01), greater than threefold higher 24-h urine excretion (WT mice: 1.3 +/- 0.1 ml vs. Agtr1a(-/-) mice: 5.9 +/- 0.7 ml, P %26lt; 0.01), and markedly decreased urine osmolality (WT mice: 1,834 +/- 86 mosM/kg vs. Agtr1a(-/-) mice: 843 +/- 170 mosM/kg, P %26lt; 0.01), without significant changes in 24-h urinary Na+ excretion. These responses in Agtr1a(-/-) mice were associated with lower basal plasma AVP (WT mice: 105 +/- 8 pg/ml vs. Agtr1a(-/-) mice: 67 +/- 6 pg/ml, P %26lt; 0.01) and decreases in total lysate and membrane aquaporin-2 (AQP2; 48.6 +/- 7% of WT mice, P %26lt; 0.001) and adenylyl cyclase isoform III (55.6 +/- 8% of WT mice, P %26lt; 0.01) proteins. Although 24-h water deprivation increased plasma AVP to the same levels in both strains, 24-h urine excretion was still higher, whereas urine osmolality remained lower, in Agtr1a(-/-) mice (P %26lt; 0.01). Water deprivation increased total lysate AQP2 proteins in the inner medulla but had no effect on adenylyl cyclase III, phosphorylated MAPK ERK1/2, and membrane AQP2 proteins in Agtr1a(-/-) mice. Furthermore, infusion of DDAVP for 2 wk was unable to correct the urine-concentrating defects in Agtr1a(-/-) mice. These results demonstrate that AT(1a) receptor-mediated ANG II signaling is required to maintain tonic AVP release and regulate V-2 receptor-mediated responses to water deprivation in the inner medulla.

• 出版日期2012-9