VASOPRESSIN V-2 RECEPTOR MESSENGER-RNA EXPRESSION AND CAMP ACCUMULATION IN AGING RAT-KIDNEY

The ability of the kidney to regulate water balance is impaired with a ge, although the secretion of vasopressin is maintained in senescent a nimals. This suggests that the cellular response to antidiuretic hormo ne is reduced in aging kidney. To test this hypothesis, the relationsh ip between the expression of the vasopressin V-2 receptor mRNA and ade nosine 3',5'-cyclic monophosphate (cAMP) accumulation was investigated in the medullary thick ascending limb of Henle's loop (MTAL) of adult and aging rats. Tubular suspensions of MTAL were prepared from 10- an d 30-mo-old female WAG/Rij rats. The accumulation of cAMP for maximal concentration of vasopressin was 34% larger in adult than in old anima ls (9.5 +/- 0.5 pmol/4 min, n = 16, and 7.1 +/- 0.6 pmol/4 min, n = 12 , respectively). The concentration of vasopressin corresponding to hal f-maximal stimulation was similar in the two groups (0.66 +/- 0.20 and 0.52 +/- 0.09 nmol, n = 5, in adult and old animals), indicating comp arable sensitivity of the renal cells with age. The age-related impair ed response to vasopressin of the V-2 receptor was specific for female s and was not observed in males. Direct stimulation of adenylyl cyclas e by forskolin induced a comparable accumulation of cAMP in adult and senescent rats. The V-2 receptor mRNA level in the MTAL was constant b etween 10 and 30 mo whether the animals were normally hydrated or dehy drated for 2 days. These data indicate that, in MTAL, the age-related impaired cAMP accumulation by vasopressin would be linked to a change either in the translation of V-2 mRNA or in posttranslational processi ng mechanisms or in the coupling between the V-2 receptor and adenylyl cyclase.