Diminished adenylate cyclase activity and aquaporin 2 expression in acute renal failure rats.
BACKGROUND
The present study was aimed at investigating the changes of aquaporin 2 (AQP2) expression and its underlying mechanisms in ischemic acute renal failure (ARF).


METHODS
ARF was induced by clamping the both renal arteries for 60 minutes in rats. Two or seven days later, AQP2 expression and trafficking were determined in the kidney by Western blot analysis and immunohistochemistry. The activity of adenylate cyclase was also measured.


RESULTS
The urinary flow rates in ARF-2 and ARF-7 day were significantly increased in association with decreases of urine osmolality. While there was decreased expression of AQP2 in the cortex, outer medulla, and inner medulla in ARF, it was most pronounced in the outer medulla. The AQP2 expression was reduced in the apical membrane-enriched fraction as well the subapical vesicle-enriched fraction in ARF; however, the degree was greater in the former than in the latter. Immunohistochemical study also showed a markedly decreased expression of AQP2 in the collecting duct in ARF. cAMP generation in response to arginine vasopressin (AVP) in the kidney was attenuated in ARF, most prominently in the outer medulla. cAMP generation in the outer medulla in response to forskolin was not affected, but sodium fluoride was significantly blunted in ARF.


CONCLUSIONS
The AVP-stimulated adenylate cyclase activity is impaired in ARF, secondary to a defect at the level of the G protein. The expression of AQP2 was reduced as a consequence, which may in part account for urinary concentration defect in ARF.
Kim
S W
SW
Department of Internal Medicine, Chonnam University Medical School, Kwangju, Korea.
Jeon
Y S
YS
Lee
J U
JU
Kang
D G
DG
Kook
H
H
Ahn
K Y
KY
Kim
S Z
SZ
Cho
K W
KW
Kim
N H
NH
Han
J S
JS
Choi
K C
KC
D058186:Acute Kidney Injury / Q000378:metabolism* / Q000503:physiopathology; D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D051399:Aquaporin 2; D051403:Aquaporin 6; D020346:Aquaporins / Q000737:chemistry / Q000378:metabolism*; D007150:Immunohistochemistry; D007668:Kidney / Q000503:physiopathology; D008297:Male; D008970:Molecular Weight; D051381:Rats; D017207:Rats, Sprague-Dawley
C496025:Aqp2 protein, rat; D051399:Aquaporin 2; D051403:Aquaporin 6; D020346:Aquaporins; D000262:Adenylyl Cyclases