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1 Service de Biologie Cellulaire, Commissariat à l'Énergie Atomique/Saclay, F-91191 Gif-sur-Yvette, France; 2 Division of Nephrology and Hypertension, University Hospital, CH-3010 Berne, Switzerland; 3 Assistance Publique-Hôpitaux de Paris, Hôpital Sainte-Périne, F-75781 Paris; and 4 Institut National de la Santé et de la Recherche Médicale U76, Institut National de Transfusion Sanguine, F-75015 Paris, France
Senescent female WAG/Rij rats exhibit polyuria without obvious renal disease or defects in vasopressin plasma level or V2 receptor mRNA expression. Normalization of urine flow rate by 1-desamino-8-D-arginine vasopressin (dDAVP) was investigated in these animals. Long-term dDAVP infusion into 30-mo-old rats reduced urine flow rate and increased urine osmolality to levels comparable to those in control 10-mo-old rats. The maximal urine osmolality in aging rat kidney was, however, lower than that in adult kidney, despite supramaximal administration of dDAVP. This improvement involved increased inner medullary osmolality and urea sequestration. This may result from upregulation of UT-A1, the vasopressin-regulated urea transporter, in initial inner medullary collecting duct (IMCD), but not in terminal IMCD, where UT-A1 remained low. Expression of UT-A2, which contributes to medullary urea recycling, was greatly increased. Regulation of IMCD aquaporin (AQP)-2 (AQP2) expression by dDAVP differed between adult and senescent rats: the low AQP2 abundance in senescent rats was normalized by dDAVP infusion, which also improved targeting of the channel; in adult rats, AQP2 expression was unaltered, suggesting that IMCD AQP2 expression is not regulated by dDAVP directly. Increased AQP3 expression in senescent rats may also be involved in improved urine-concentrating capacity owing to higher basolateral water and urea reabsorption capacity.
papilla osmolality; nitric oxide synthase; glucocorticoids; 1-desamino-8-D-arginine vasopressin
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