期刊
KIDNEY INTERNATIONAL
卷 58, 期 2, 页码 701-711出版社
BLACKWELL SCIENCE INC
DOI: 10.1046/j.1523-1755.2000.00216.x
关键词
collecting duct; nephrotoxicity; vasopressin; proximal tubules; medullary hypertonicity
Background. Cisplatin (CP)-induced polyuria in rats is attributed to decreased medullary hypertonicity and/or an endorgan 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 mu g/g vs. 2.52 +/- 0.43 and 1.87 +/- 0.84 mu g/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.
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