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

Abstract

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.

Food restriction prevents age-related polyuria by vasopressin-dependent recruitment of aquaporin-2

“…AQP2 targeting to the apical membrane is tightly regulated by arginine vasopressin (AVP), which induces fusion of subapical vesicles containing AQP2 with plasma membrane (13,27). This process occurs through AVP binding to its V 2 receptor in the basolateral membrane, activation of the cAMP signaling pathway, and phosphorylation of AQP2 at serine-256 by protein kinase A (22).Polyuria with reduced urine osmolality affects elderly humans and rodents (5,6,9,42). In some strains of rats, this age-related defect has been attributed to a loss of nephrons or an impaired AVP secretion (25,32,40,46,53,55).…”

“…Polyuria with reduced urine osmolality affects elderly humans and rodents (5,6,9,42). In some strains of rats, this age-related defect has been attributed to a loss of nephrons or an impaired AVP secretion (25,32,40,46,53,55).…”

Gestational hypoxia and programming of disease

“…Declining urine concentrating capacity has been observed in elderly humans (Rowe et al, 1976;Phillips et al, 1984) as well as studies of ageing animals (Bengele et al, 1981;Perucca et al, 2007;Singh et al, 2011). This decline is multifactorial, linked to progressive loss of functional glomeruli, reduced secretion of vasopressin (Tian et al, 2004), impaired cellular response to vasopressin (Beck & Yu, 1982;Corman et al, 1992;Geelen & Corman, 1992) and reduced GFR (Levinsky et al, 1959). As urine osmolality tended to be lower in 4-month-old male hypoxia-exposed offspring compared to control counterparts, an early onset decline in urine concentrating capacity may have occurred in these animals.…”

“…Reduced urine concentrating capacity is also used as clinical marker of early renal failure as it is observed in patients with reduced GFR . This has previously been attributed to progressive loss of glomeruli, impaired vasopressin secretion or responsiveness (Beck & Yu, 1982), and decreased AQP2 expression in the collecting ducts (Tian et al, 2004).…”

“…Other groups have created more severe models of total water dehydration by depriving animals of water for 2-4 days to yield a urine-concentrating deficit (Beck & Yu, 1982;Steiner & Phillips, 1988;Geelen & Corman, 1992;Terashima et al, 1998). However this is associated with substantial body weight loss, hypovolemia and hypernatremia.…”