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/kgH2O in adult rats and 12.8 ± 0.8 ml/24 h and 1,042 ± 44 mosmol/kgH2O in senescent animals. Vasopressin V2 receptor mRNA did not significantly differ between 10 and 30 mo, and [3H]vasopressin binding sites in membrane papilla were reduced by 30%. The cAMP content of the papilla was unchanged with age, whereas papillary osmolality was significantly lowered in senescent animals. The expression of aquaporin-1 (AQP1) and -4 was mostly unaltered from 10 to 30 mo. In contrast, aquaporin-2 (AQP2) and -3 (AQP3) expression was downregulated by 80 and 50%, respectively, and AQP2 was markedly redistributed into the intracellular compartment, in inner medulla of senescent animals, but not in renal cortex. These results indicate that age-related polyuria is associated with a downregulation of AQP2 and AQP3 expression in the medullary collecting duct, which is independent of vasopressin-mediated cAMP accumulation.
The Aging Kidney: Increased Susceptibility to Nephrotoxicity
