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Articles in PresS, published online ahead of print August 13, 2002
Am J Physiol Renal Physiol, 10.1152/ajprenal.00167.2002
Submitted on April 30, 2002
Accepted on August 7, 2002
1 DBCM/SBCe, Service de Biologie Cellulaire, CEA/Saclay, Gif-sur-Yvette, France
2 Division of Nephrology and Hypertension, University Hospital, Berne, Switzerland
3 DBCM/SBCe, Service de Biologie Cellulaire, CEA/Saclay, Gif-sur-Yvette, France; Hopital Sainte-Perine, Assistance Publique-Hopitaux de Paris, Paris, France
4 DBCM/SBCe, Service de Biologie Cellulaire, CEA/Saclay, Gif-sur-Yvette, France; INSERM U76, Institut National de Transfusion Sanguine, Paris, France
* To whom correspondence should be addressed. E-mail: trinh{at}idf.inserm.fr.
Senescent female WAG/Rij rats exhibit polyuria without obvious renal disease or defects in vasopressin plasma level or in V2-receptor mRNA expression. Normalization of urine flow rate by dDAVP was investigated in these animals. Long-term dDAVP infusion to 30-month-old rats reduced urine flow rate and increased urine osmolality to values comparable to control 10-month-old rats. The maximal urine osmolality reached by aging rat kidney was, however, lower than that of the adult one despite supramaximal administration of dDAVP. This improvement involved increased inner medulla osmolality and urea sequestration. This may result from the upregulation of UT-A1, the vasopressin-regulated urea transporter, observed in initial inner medullary collecting duct (IMCD), but not in terminal IMCD, where UT-A1 remained low. The expression of UT-A2 which contributes to medullary urea recycling was greatly increased. Regulation of IMCD AQP2 expression by dDAVP differed between adult and senescent rats: the low AQP2 abundance observed 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 concentration capacity owing to higher basolateral water and urea reabsorption capacity.
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