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

Mice lacking AT(1A) receptors for ANG II have a defect in urinary concentra tion manifested by an inability to increase urinary osmolality to levels se en in controls after thirsting. This defect results in extreme serum hypert onicity during water deprivation. In the basal state, plasma vasopressin le vels are similar in wild-type controls and Agtr1a -/- mice. Plasma vasopres sin levels increase normally in the AT(1A) 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 th at the absence of AT(1A) receptors is associated with a modest reduction in the distance from the kidney surface to the tip of the papilla. However, t his structural abnormality seems to play little role in the urinary concent rating defect in Agtr1a -/- mice since the impairment is largely reproduced in wild-type mice by treatment with an AT(1)-receptor antagonist. These st udies demonstrate a critical role for the AT(1A) receptor in maintaining in ner medullary structures in the kidney and in regulating renal water excret ion.