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 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 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 that 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, 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 AT(1)-receptor antagonist. These studies demonstrate a critical role for the AT(1A) receptor in maintaining inner medullary structures in the kidney and in regulating renal water excretion.
Oliverio
M I
MI
Department of Medicine, Duke University, and Veterans Affairs Medical Centers, Durham, NC 27710, USA.
Delnomdedieu
M
M
Best
C F
CF
Li
P
P
Morris
M
M
Callahan
M F
MF
Johnson
G A
GA
Smithies
O
O
Coffman
T M
TM
D057911:Angiotensin Receptor Antagonists; D000818:Animals; D001835:Body Weight; D003894:Deamino Arginine Vasopressin / Q000494:pharmacology; D005260:Female; D005838:Genotype; D007668:Kidney / Q000033:anatomy & histology / Q000378:metabolism*; D007671:Kidney Concentrating Ability / Q000187:drug effects / Q000502:physiology*; D019808:Losartan / Q000494:pharmacology; D008297:Male; D051379:Mice; D009994:Osmolar Concentration; D044140:Receptor, Angiotensin, Type 1; D011945:Receptors, Angiotensin / Q000172:deficiency* / Q000235:genetics; D014556:Urine / Q000737:chemistry; D014563:Urodynamics; D014667:Vasopressins / Q000097:blood; D014867:Water / Q000378:metabolism* / Q000494:pharmacology; D014868:Water Deprivation
D057911:Angiotensin Receptor Antagonists; D044140:Receptor, Angiotensin, Type 1; D011945:Receptors, Angiotensin; D014867:Water; D014667:Vasopressins; D003894:Deamino Arginine Vasopressin; D019808:Losartan