Vasopressin and renin response to dehydration in aged rats

Sladek, Celia D.; McNeill, Thomas H.; Gregg, Christine M.; Blair, Martha L.; Baggs, Raymond B.

doi:10.1016/0197-4580(81)90038-5

Cited by 68 publications

(36 citation statements)

References 37 publications

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“…However, conflicting results have been reported using different strains of rats. For example, decreased AVP secretion in response to dehydration and a greater depletion of AVP content in the posterior pituitary were observed in 30-mo-old F344 rats (39,44) but not in F344BN rats (21). Absent increases in AVP mRNA content in response to dehydration were also reported in aged rats (40).…”

Section: Discussionmentioning

confidence: 72%

“…Similarly, decreased AVP secretion, resulting in reduced collecting duct osmotic permeability and increased water excretion, is supported by some studies that showed decreased pituitary and plasma AVP concentrations in aging rats but not by others (36,54). Some of these conflicting results may reflect the variety of different species, strains, and ages of animals used in aging studies from different laboratories (3,9,10,12,35,39,51,52). 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).…”

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confidence: 79%

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

Tian¹,

Serino²,

Verbalis³

2004

American Journal of Physiology-Renal Physiology

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Tian, Ying, Ryota Serino, and Joseph G. Verbalis. Downregulation of renal vasopressin V2 receptor and aquaporin-2 expression parallels age-associated defects in urine concentration. Am J Physiol Renal Physiol 287: F797-F805, 2004. First published June 22, 2004 10.1152/ajprenal.00403.2003.-Renal concentrating ability is known to be impaired with aging. The antidiuretic hormone AVP plays an important role in renal water excretion by regulating the membrane insertion and abundance of the water channel aquaporin-2 (AQP2); this effect is primarily mediated via the V2 subtype of the AVP receptor (V2R). This study evaluated the hypothesis that decreased renal sensitivity to AVP, with subsequent altered renal AQP2 expression, contributes to the reduced urinary concentrating ability with aging. Our results show that under baseline conditions, urine osmolality is significantly lower in aged Fischer 344 and Brown-Norway F1 hybrid (F344BN) rats despite equivalent plasma AVP concentrations as in young rats. Levels of kidney V2R mRNA expression and AQP2 abundances were also significantly decreased in aged F344BN rats, as was AQP2 immunostaining in collecting duct cells. In response to moderate water restriction, urine osmolality increased by significantly lesser amounts in aged F344BN rats compared with young rats despite similar increases in plasma AVP levels. Moderate water restriction induced equivalent relative increases in renal AQP2 abundances in all age groups but resulted in significantly lower abundances in total kidney AQP2 protein in aged compared with young F344BN rats. These results therefore demonstrate a functional impairment of renal concentrating ability in aged F344BN rats that is not due to impaired secretion of AVP but rather appears to be related to impaired responsiveness of the kidney to AVP that is secondary, at least in part, to a downregulation of renal V2R expression and AQP2 abundance.aging; aquaporins; kidney AN AGE-RELATED DECLINE IN urinary concentrating ability has been documented in experimental animals as well as in elderly humans (2,3,13,16,17,20,30,31). Both the increase in urinary concentration and the decrease in urine volume that are characteristically observed after water deprivation are reduced in aged compared with young humans. For example, maximum urine osmolality was found to be significantly lower in elderly subjects (aged 60 -79) than in young subjects (aged 20 -39) following a 24-h period of water deprivation (882 Ϯ 49 vs. 1,109 Ϯ 22 mosmol/kgH 2 O, respectively, P Ͻ 0.01) (37). Normally, such decreases in urinary concentrating ability are easily compensated for by increased fluid intake stimulated by neural thirst pathways. However, the elderly also have a decreased sensation of thirst in response to dehydration, and as a result they drink less water following periods of dehydration (34). These combined neural and kidney impairments make elderly humans much more susceptible to developing life-threatening degrees of hyperosmolality and hypovolemia in response to periods of deh...

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Section: Discussionmentioning

confidence: 72%

mentioning

confidence: 79%

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

Tian¹,

Serino²,

Verbalis³

2004

American Journal of Physiology-Renal Physiology

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“…However, the licking behavior examined under these conditions could be considered more consummatory than instrumental. As mentioned previously, aged rats are more sensitive to water restriction and exhibit altered fluid regulatory mechanisms compared to younger rats [27,34]. Because of this, and because the motor demands of licking are less than those involved in operant leverpressing tasks, the number of licks emitted during these 6 min sessions should not be considered analogous to other motor measurements.…”

Section: Discussionmentioning

confidence: 96%

“…Rats were trained to lick water from a disc that was attached to an isometric force transducer. While aged rats exhibited a greater number of licks per session (perhaps due to decreased tolerance to water restriction [27,34]), tongue motility as quantified by licks-persecond was significantly diminished in this group compared to the young group. This finding is consistent with studies reporting diminished tongue motility in elderly volunteers who performed an analogous repetitive tongue movement task [16].…”

Section: Introductionmentioning

confidence: 99%

Age-related changes in orolingual motor function in F344 vs F344/BN rats

Zhang¹,

Bethel²,

Smittkamp³

et al. 2008

Physiology & Behavior

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Normal aging is associated with both locomotor and orolingual motor deficits. Preclinical studies of motor function in normal aging, however, have focused primarily on locomotor activity. The purpose of this study was to measure age-related changes in orolingual motor function and compare these changes between two rat strains commonly used in aging studies: Fischer 344 (F344) and Fischer 344/Brown Norway hybrid (F344/BN) rats. Rats (6-, 12-, 18-and 24-months of age) were trained to lick water from an isometric force-sensing operandum so that the number of licks per session, licking rhythm (licks/second) and lick force could be measured. In both strains, the number of licks per session was greatest in the oldest group, while this measure was greater for F344/BN rats at all ages. Peak tongue force increased with age in F344/BN rats, did not change with age in the F344 rats, and was greater for the F344/BN rats at all ages. Both strains exhibited an age-related slowing of licking rhythm beginning with the 18-month-old group. These findings suggest that despite lifespan differences between these two rat strains, diminished tongue motility emerges at the same age.

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“…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).…”

mentioning

confidence: 99%

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

Combet

Teillet

Geelen

et al. 2001

American Journal of Physiology-Renal Physiology

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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 ...

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Vasopressin and renin response to dehydration in aged rats

Cited by 68 publications

References 37 publications

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

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

Age-related changes in orolingual motor function in F344 vs F344/BN rats

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

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