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Am J Physiol Renal Physiol 287: F797-F805, 2004. First published June 22, 2004; doi:10.1152/ajprenal.00403.2003
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Downregulation of renal vasopressin V2 receptor and aquaporin-2 expression parallels age-associated defects in urine concentration

Ying Tian,1 Ryota Serino,2 and Joseph G. Verbalis1

1Division of Endocrinology and Metabolism, Department of Medicine, Georgetown University, Washington, District of Columbia 20007; and 2Department of Physiology, University of Occupational and Environmental Health, Kitakyushu, Japan 807-8555

Submitted 13 November 2003 ; accepted in final form 7 June 2004

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



Address for reprint requests and other correspondence: Y. Tian, Division of Endocrinology and Metabolism, Bldg. D, Rm. 232, Georgetown Univ., 4000 Reservoir Road NW, Washington, DC 20007 (E-mail: tiany{at}georgetown.edu)




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