Expression of renal aquaporins 1, 2, and 3 in a rat model of cisplatin-induced polyuria.
BACKGROUND
Cisplatin (CP)-induced polyuria in rats is attributed to decreased medullary hypertonicity and/or an end-organ resistance to vasopressin. However, the roles of renal aquaporins (AQPs) have not yet been explored.


METHODS
Male Sprague-Dawley rats (230 to 245 g) received either a single injection of CP (5 mg/kg, N = 4) or saline (N = 4) intraperitoneally five days before sacrifice. Urine, blood, and kidney samples were analyzed.


RESULTS
Platinum accumulated in the cortex and outer medulla of CP-treated rats (39.05 +/- 7.50 and 36.48 +/- 12.44 microg/g vs. 2.52 +/- 0.43 and 1.87 +/- 0.84 microg/g dry tissue in controls, respectively). Histologically, tubular damage and decreased AQP1 immunolabeling were detected in the S3 segment of proximal tubules. CP treatment caused 4.4- and 4.8-fold increases, respectively, in blood urea nitrogen and urine volume, and a 4. 4-fold decrease in urine osmolality. Immunoblots showed that AQP2 and AQP3 were significantly reduced to 33 +/- 10% (P < 0.001) and 69 +/- 11% (P < 0.05), respectively, in the inner medulla of CP-treated rats. Immunocytochemical analysis showed a decrease in AQP2 labeling in the inner medulla of CP-treated rats. Northern hybridization revealed a 33 +/- 11% (P < 0.002) decrease in AQP2 mRNA expression in the inner medulla of CP-treated rats. AQP1 protein expression levels were modestly (67 +/- 7%, P = 0.057) and significantly (53 +/- 13%, P < 0.007) decreased in outer and inner medullae, respectively, of CP-treated rats.


CONCLUSIONS
CP-induced polyuria in rats is associated with a significant decrease in the expression of collecting duct (AQP2 and AQP3) and proximal nephron and microvascular (AQP1) water channels in the inner medulla.
Kishore
B K
BK
Departments of Internal Medicine, Molecular Genetics, Biochemistry and Microbiology, College of Medicine, University of Cincinnati, Ohio 45267-0585, USA. B.K.Kishore@uc.edu
Krane
C M
CM
Di Iulio
D
D
Menon
A G
AG
Cacini
W
W
D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity; D051398:Aquaporin 1; D051399:Aquaporin 2; D051400:Aquaporin 3; D051403:Aquaporin 6; D020346:Aquaporins / Q000032:analysis / Q000235:genetics*; D001806:Blood Urea Nitrogen; D015152:Blotting, Northern; D001835:Body Weight; D002945:Cisplatin / Q000633:toxicity; D004195:Disease Models, Animal; D015870:Gene Expression / Q000502:physiology; D015151:Immunoblotting; D007685:Kidney Tubules, Collecting / Q000737:chemistry / Q000502:physiology; D007687:Kidney Tubules, Proximal / Q000737:chemistry / Q000502:physiology; D008297:Male; D010984:Platinum / Q000032:analysis; D011141:Polyuria / Q000139:chemically induced / Q000503:physiopathology*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D016482:Urinalysis; D014667:Vasopressins / Q000378:metabolism
D000970:Antineoplastic Agents; C496022:Aqp1 protein, rat; C496025:Aqp2 protein, rat; C496029:Aqp3 protein, rat; D051399:Aquaporin 2; D051403:Aquaporin 6; D020346:Aquaporins; D012333:RNA, Messenger; D014667:Vasopressins; D051398:Aquaporin 1; D051400:Aquaporin 3; D010984:Platinum; D002945:Cisplatin