Diminished renal expression of aquaporin water channels in rats with experimental bilateral ureteral obstruction.
Whether postobstructive diuresis could be related to altered regulation of aquaporin (AQP) water channels in the kidney was investigated. Male Sprague-Dawley rats underwent bilateral obstruction of the proximal ureters for 48 h. The renal expression of AQP1 to AQP4 proteins was then determined by Western blot and immunohistochemical analyses. For elucidation of the primary impairment in the upstream pathway leading to the expression of cAMP-mediated AQP channels, the expression of G(salpha) and that of adenylyl cyclase were also determined. For some rats, the obstruction was released for collection of urine samples. After the ureteral obstruction, the urinary flow rate was increased and free water reabsorption was decreased. In the obstructed kidneys, the expression of AQP1 to AQP3 was decreased in the cortex, outer medulla, and inner medulla, whereas that of AQP4 was decreased in the inner medulla. Immunoreactivities for AQP1 to AQP4 were also decreased in the obstructed kidneys. The protein expression of G(salpha) was decreased in the cortex, outer medulla, and inner medulla, whereas that of adenylyl cyclase VI was decreased in the outer and inner medullae. cAMP generation stimulated by arginine vasopressin was decreased in the cortex, outer medulla, and inner medulla. cAMP generation in response to forskolin was decreased in the outer and inner medullae, whereas that in response to sodium fluoride was decreased in the cortex, outer medulla, and inner medulla. These results suggest that a reduced abundance of AQP water channels in the kidney accounts in part for postobstructive diuresis. The primary impairment of AQP channels that are regulated via the arginine vasopressin/cAMP pathway may lie at the level of G proteins and adenylyl cyclase itself.
Kim
Soo Wan
SW
Chonnam National University Research Institute of Medical Sciences, Gwangju, Korea.
Cho
Sam Hyeon
SH
Chonnam National University Research Institute of Medical Sciences, Gwangju, Korea.
Oh
Bong Suk
BS
Chonnam National University Research Institute of Medical Sciences, Gwangju, Korea.
Yeum
Chung Ho
CH
Chonnam National University Research Institute of Medical Sciences, Gwangju, Korea.
Choi
Ki Chul
KC
Chonnam National University Research Institute of Medical Sciences, Gwangju, Korea.
Ahn
Kyu Youn
KY
Chonnam National University Research Institute of Medical Sciences, Gwangju, Korea.
Lee
Jongun
J
Chonnam National University Research Institute of Medical Sciences, Gwangju, Korea.
D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D020346:Aquaporins / Q000378:metabolism*; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000378:metabolism; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000378:metabolism; D007668:Kidney / Q000378:metabolism*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D051437:Renal Insufficiency / Q000378:metabolism; D014517:Ureteral Obstruction / Q000378:metabolism*
D020346:Aquaporins; D007527:Isoenzymes; D019205:GTP-Binding Protein alpha Subunits, Gs; D000262:Adenylyl Cyclases