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.
Departments of Internal Medicine, Molecular Genetics, Biochemistry and Microbiology, College of Medicine, University of Cincinnati, Ohio 45267-0585, USA. B.K.Kishore@uc.edu
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Kishore
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Krane
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Di Iulio
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Menon
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Cacini
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