Expression of renal aquaporins 1, 2, and 3 in a rat model of cisplatin-induced polyuria

Kidney Int. 2000 Aug;58(2):701-11. doi: 10.1046/j.1523-1755.2000.00216.x.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antineoplastic Agents / toxicity
  • Aquaporin 1
  • Aquaporin 2
  • Aquaporin 3
  • Aquaporin 6
  • Aquaporins / analysis
  • Aquaporins / genetics*
  • Blood Urea Nitrogen
  • Blotting, Northern
  • Body Weight
  • Cisplatin / toxicity
  • Disease Models, Animal
  • Gene Expression / physiology
  • Immunoblotting
  • Kidney Tubules, Collecting / chemistry
  • Kidney Tubules, Collecting / physiology
  • Kidney Tubules, Proximal / chemistry
  • Kidney Tubules, Proximal / physiology
  • Male
  • Platinum / analysis
  • Polyuria / chemically induced
  • Polyuria / physiopathology*
  • RNA, Messenger / analysis
  • Rats
  • Rats, Sprague-Dawley
  • Urinalysis
  • Vasopressins / metabolism

Substances

  • Antineoplastic Agents
  • Aqp1 protein, rat
  • Aqp2 protein, rat
  • Aqp3 protein, rat
  • Aquaporin 2
  • Aquaporin 6
  • Aquaporins
  • RNA, Messenger
  • Vasopressins
  • Aquaporin 1
  • Aquaporin 3
  • Platinum
  • Cisplatin