Molecular mechanisms of impaired urinary concentrating ability in glucocorticoid-deficient rats.
The purpose of this study was to examine urinary concentrating ability and protein expression of renal aquaporins and ion transporters in glucocorticoid-deficient (GD) rats in response to water deprivation as compared with control rats. Rats underwent bilateral adrenalectomies, followed only by aldosterone replacement (GD) or both aldosterone and dexamethasone replacement (control). As compared with control rats, the GD rats demonstrated a decrease in cardiac output and mean arterial pressure. In response to 36-h water deprivation, GD rats demonstrated significantly greater urine flow rate and decreased urine osmolality as compared with control rats at comparable serum osmolality and plasma vasopressin concentrations. The initiator of the countercurrent concentrating mechanism, the sodium-potassium-2 chloride co-transporter, was significantly decreased, as was the medullary osmolality in the GD rats versus control rats. There was also a decrease in inner medulla aquaporin-2 (AQP2) and urea transporter A1 (UT-A1) in GD rats as compared with control rats. There was a decrease in outer medulla Gsalpha protein, an important factor in vasopressin-mediated regulation of AQP2. Immunohistochemistry studies confirmed the decreased expression of AQP2 and UT-A1 in kidneys of GD rats as compared with control. In summary, impairment in the urinary concentrating mechanism was documented in GD rats in association with impaired countercurrent multiplication, diminished osmotic equilibration via AQP2, and diminished urea equilibration via UT-A1. These events occurred primarily in the relatively oxygen-deficient medulla and may have been initiated, at least in part, by the decrease in mean arterial pressure and thus renal perfusion pressure in this area of the kidney.
Chen
Yung-Chang
YC
Division of Renal Diseases and Hypertension, University of Colorado Health Sciences Center, 4200 East 9th Avenue, Box B173, Denver, CO 80262, USA.
Cadnapaphornchai
Melissa A
MA
Summer
Sandra N
SN
Falk
Sandor
S
Li
Chunling
C
Wang
Weidong
W
Schrier
Robert W
RW
D000818:Animals; D005938:Glucocorticoids / Q000172:deficiency*; D006439:Hemodynamics; D007668:Kidney / Q000378:metabolism*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D014556:Urine; D014868:Water Deprivation
D005938:Glucocorticoids