Abnormal water metabolism in mice lacking the type 1A receptor for ANG II

Abstract

Mice lacking AT1Areceptors for ANG II have a defect in urinary concentration manifested by an inability to increase urinary osmolality to levels seen in controls after thirsting. This defect results in extreme serum hypertonicity during water deprivation. In the basal state, plasma vasopressin levels are similar in wild-type controls and Agtr1a −/− mice. Plasma vasopressin levels increase normally in the AT1A receptor-deficient mice after 24 h of water deprivation, suggesting that the defect in urine concentration is intrinsic to the kidney. Using magnetic resonance microscopy, we find that the absence of AT1A receptors is associated with a modest reduction in the distance from the kidney surface to the tip of the papilla. However, this structural abnormality seems to play little role in the urinary concentrating defect in Agtr1a −/− mice since the impairment is largely reproduced in wild-type mice by treatment with an AT1-receptor antagonist. These studies demonstrate a critical role for the AT1A receptor in maintaining inner medullary structures in the kidney and in regulating renal water excretion.