Downregulation of aquaporin-2 and-3 in aging kidney is independent of V-2 vasopressin receptor

The mechanisms underlying age-related polyuria were investigated in 10- and 30-mo-old female WAG/Rij rats. Urinary volume and osmolality were 3.9 +/- 0.3 ml/24 h and 2,511 +/- 54 mosmol/kgH(2)O in adult rats and 12.8 +/- 0.8 ml/24 h and 1,042 +/- 44 mosmol/kgH(2)O in senescent animals. Vasopressin V -2 receptor mRNA did not significantly differ between 10 and 30 mo, and [H- 3]vasopressin binding sites in membrane papilla were reduced by 30%. The cA MP content of the papilla was unchanged with age, whereas papillary osmolal ity was significantly lowered in senescent animals. The expression of aquap orin-1 (AQP1) and -4 was mostly unaltered from 10 to 30 mo. In contrast, aq uaporin-2 (AQP2) and -3 (AQP3) expression was down-regulated by 80 and 50%, respectively, and AQP2 was markedly redistributed into the intracellular c ompartment, in inner medulla of senescent animals, but not in renal cortex. These results indicate that age-related polyuria is associated with a down regulation of AQP2 and AQP3 expression in the medullary collecting duct, wh ich is independent of vasopressin-mediated cAMP accumulation.