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

Abstract

The mechanisms underlying the prevention of age-related polyuria by chronic food restriction were investigated in female WAG/Rij rats. The decreased osmolality of renal papilla observed in senescent rats was not corrected by food restriction. A reduced urea content in the inner medulla of senescent rats, fed ad libitum or food-restricted, was suggested by the marked decrease in expression of UT-A1 and UT-B1 urea transporters. Aquaporin-2 (AQP2) downregulation in the inner medulla of senescent rats was partially prevented by food restriction. Both AQP2 and the phosphorylated form of AQP2 (p-AQP2), the presence of which was diffuse within the cytoplasm of collecting duct principal cells in normally fed senescent rats, were preferentially targeted at the apical region of the cells in food-restricted senescent animals. Plasma vasopressin (AVP) was similar in 10-and 30-mo-old rats fed ad libitum, but was doubled in foodrestricted 30-mo-old rats. This study indicates that 1) kidney aging is associated with a marked decrease in AQP2, UT-A1, and UT-B1 expression in the inner medulla and a reduced papillary osmolality; and 2) the prevention of age-related polyuria by chronic food restriction occurs through an improved recruitment of AQP2 and p-AQP2 to the apical membrane in inner medulla principal cells, permitted by increased plasma AVP concentration. kidney aging; phosphorylation; urea transporters IN MAMMALIAN KIDNEY, MOST of filtered water is reabsorbed through the water channel aquaporin-1 (AQP1) constitutively present in the apical and basolateral membranes of the proximal tubule and thin descending limb (28,35). Final urine is concentrated along the collecting duct by water subtraction owing to the corticopapillary osmotic gradient and water permeability of principal cells, endowed by AQP2 in the apical membrane and both AQP3 and AQP4 in the basolateral membrane. 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). However, it is still observed in senescent female WAG/Rij rats that remain free of glomerulosclerosis and have a normal number of nephrons, renal blood flow, and single renal filtration rates (10-12). Plasma AVP concentration, V 2 -receptor expression, and intracellular cAMP content in the papilla are also maintained in these old rats (15,30). By contrast, senescent female WAG/Rij rats exhibited a low papillary osmolality and a weak expression of AQP2 and AQP3, whereas expression of AQP1 and AQP4 was unaltered (30). This suggested a low water permeability of the ...

Downregulation of renal vasopressin V2 receptor and aquaporin-2 expression parallels age-associated defects in urine concentration

“…Both of these parameters are also strongly influenced by AVP through the V2R. In this regard, previous studies showed reduced AVP-dependent reabsorption of sodium by thick ascending limb of Henle's loop in senescent mice (14) and decreased medullary abundances of UT-A1 and UT-B1 urea transporters resulting in decreased papillary urea concentrations and osmolality in aged WAG/Rij rats (7,8,48). Thus each of these factors in addition to AQP2 expression may contribute to the observed changes in urinary concentration with aging, and further studies will be needed to assess the relative contributions of each of these factors under different physiological conditions in F344BN rats.…”

“…Nonetheless, most studies are consistent with a reduced renal cellular response to AVP, leading to decreased water permeability of the collecting duct, as an important contributor to age-associated impairments in renal concentrating ability (5,6,19). Studies showing reduced AVPdependent reabsorption of sodium by the thick ascending limb of Henle's loop in senescent mice (14) and decreased expression of the AVP-stimulated urea transporter UT-A1 in aged female WAG/Rij rats (7,8,48) further support an altered renal responsiveness to AVP with aging.AVP plays a critical role in the regulation of renal water excretion. AVP increases water permeability in the collecting duct of the kidney by regulating membrane insertion and abundance of the water channel aquaporin-2 (AQP2).…”

Age-Related Increase in Plasma Urea Level and Decrease in Fractional Urea Excretion

“…Some urea transporter expressions have been studied in the aging kidney of rats. Markedly reduced kidney UT-A1, UT-A2, and UT-B1 abundances have been reported in senescent rats (27,28). Moreover, a different regional expression for UT-B1 within the inner medulla has been disclosed in the course of aging.…”

Urine-concentrating defects exacerbate with age in male offspring with a low-nephron endowment

“…AVP binds to the vasopressin 2 receptor (V2R) in the basolateral membrane of the collecting duct cells of the kidney and the eventual phosphorylation and translocation of aquaporin-2 (AQP-2) to the apical membrane increase the permeability of the collecting ducts to water, allowing for conservation of fluid (3). However, some ageing rat models reported impairment in urine-concentrating ability despite similar levels of AVP secretion, suggesting that the impairment is attributed to a de-crease in the renal expression of AQP-2 (7,41). Rats with chronic renal failure induced by a surgical reduction in renal mass have decreased urinary concentrating ability that is associated with a downregulation of AQP-2 as well (17).…”