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This Article Full Text Full Text (PDF) All Versions of this Article: 294/6/F1408    most recent 00437.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Combet, S. Articles by Verbavatz, J.-M. Search for Related Content PubMed PubMed Citation Articles by Combet, S. Articles by Verbavatz, J.-M.

Aquaporin-2 downregulation in kidney medulla of aging rats is posttranscriptional and is abolished by water deprivation

¹CEA, Institut de Biologie et Technologies de Saclay and CNRS URA 2096, Gif-sur-Yvette and LRA17V University Paris-Sud 11, Orsay; ²Laboratoire Léon-Brillouin, UMR 12 CEA/CNRS, CEA-Saclay, Gif-sur-Yvette; ³Laboratoire de Physiologie, UFR de Médecine Grange Blanche, Université Claude-Bernard Lyon I, and Exploration Fonctionnelle Endocrinienne et Métabolique, CBN, Hôpital de la Croix Rousse, Lyon; and ⁴Successful Aging Database, Boulogne-Billancourt, France

Submitted 18 September 2007 ; accepted in final form 25 March 2008

Aging kidney is associated in humans and rodents with polyuria and reduced urine concentrating ability. In senescent female WAG/Rij rats, this defect is independent of arginine-vasopressin (AVP)/V₂ receptor/cAMP pathway. It has been attributed to underexpression and mistargeting of aquaporin-2 (AQP2) water channel in the inner medullary collecting duct (IMCD). We showed previously that dDAVP administration could partially correct this defect. Since AQP2 can also be regulated by AVP-independent pathways in water deprivation (WD), we investigated AQP2 and phosphorylated AQP2 (p-AQP2) regulation in thirsted adult (10 mo old) and senescent (30 mo old) female WAG/Rij rats. Following 2-day WD, urine flow rate decreased and urine osmolality increased in both groups. However, in agreement with significantly lower cortico-papillary osmotic gradient with aging, urine osmolality remained lower in senescent animals. WD induced sixfold increase of plasma AVP in all animals which, interestingly, did not result in higher papillary cAMP level. Following WD, AQP2 and p-AQP2 expression increased hugely in 10- and 30-mo-old rats and their mistargeting in old animals was corrected. Moreover, the age-related difference in AQP2 regulation was abolished after WD. To further investigate the mechanism of AQP2 underexpression with aging, AQP2 mRNA was quantified by real-time RT-PCR. In the outer medulla, preservation of AQP2 protein expression was achieved through increased AQP2 mRNA level in senescent rats. In the IMCD, no change in AQP2 mRNA was detected with aging but AQP2 protein expression was markedly lower in 30-mo-old animals. In conclusion, there is a posttranscriptional downregulation of AQP2 with aging, which is abolished by WD.

aquaporins; urine concentration; AVP; cAMP; cGMP; phosphorylated AQP2