Effect of aging on urinary concentrating mechanism and vasopressin-dependent cAMP in rats

The effect of aging on urinary concentrating ability and the pathogenic mechanism involved were investigated in Fischer 344 rats. While the rats had free access to drinking water, 24-mo-old rats were polydipsic and polyuric compared with 6- and 12-mo-old rats. The maximum urinary concentrating ability after 40-58 h of water deprivation was not different between 6- and 12-mo-old rats (Uosmol 2,941 +/- 173 vs. 2,706 +/- 96 (SE) mosmol/kg), but it was significantly decreased in 24-mo-old rats (1,885 +/- 172 mosmol/kg, P less than 0.01). Similarly, although 5 mU/ml vasopressin increased the concentration of cAMP and papillary slices in 12-mo-old rats (delta +2.81 +/- 0.62 pmol/mg tissue, P less than 0.01), the same concentration of vasopressin failed to increase the cAMP concentration in 24-mo-old rats (delta +0.25 +/- 0.21 pmol/mg tissue, P greater than 0.05). In the adenylate cyclase preparation of renal papilla, the response to low concentrations of vasopressin was diminished in 24-mo-old rats. The dose-response curve was shifted to the right and the ED50 concentration of vasopressin was increased in 24-mo-old rats compared with 12-mo-old rats: 1.40 +/- 0.12 mU/ml vasopressin vs. 3.04 +/- 0.22. These results suggest that the decrease in vasopressin-dependent cAMP generation may in part be responsible for the impairment of urinary concentrating ability in 24-mo-old rats.