Development of urinary concentrating capacity: role of aquaporin-2 ( aqp2). Yasui, M., D. Marples, R. Belusa, A-C. Ekl[diaeresis]of, G. Celsi, S. Nielsen, and A. Aperia. Dept. of Woman and Child Health, Pediatric, St. G[diaeresis]oran's Children's Hospital, Karolinska Inst., S-11281, Stockholm, Sweden; and Department of Cell Biology, University of Aarhus, DK-8000 Aarhus C, Denmark
APStracts 3:0014F, 1996.
The capacity to concentrate urine develops progressively during postnatal life in most mammalian species. Here we have examined whether low expression of the arginine vasopressin (AVP) activated water channel aquaporin-2 (AQP2) may be a limiting factor for the concentrating capacity in the infant rats. Urine osmolality in response to 24 h dehydration increased significantly from 10 to 40 days of age. The most rapid increase occurred during the weaning period, i.e. day 15 to 20. A similar developmental pattern was observed for AQP2 mRNA levels in the renal medulla. AQP2 protein levels also increased markedly from day 10 to 40. Immuno -histochemistry revealed that AQP2 was exclusively located in collecting duct principal cells both in infant and adult rats but the signal was much weaker in infants. To further examine the relationship between urinary concentrating capacity and AQP2 expression, we treated rats with a single injection of betamethasone, which is known to accelerate maturation in several organs . 24 h after treatment there was an increase in urine osmolality, renal medullary AQP2 mRNA and AQP2 protein levels in infant but not in adult rats. A single injection of a specific V2 agonist caused within 6 hours significant increase of AQP2 mRNA in both infant and adult. The expression of the mRNA of three other transporters involved in the concentrating process, medullary Na+,K+-ATPase alpha-subunit (NKA [alpha]-1), Na,K,2Cl cotransporter (rBSC1) and epithelial chloride channel (ClC-K1) also increased during the weaning period and were upregulated by GC. We conclude that there is a well synchronized development of the many of the components that determine the concentrating capacity and that the low expression of AQP2 is one of the limiting factors for low concentrating capacity in infants.

Received 8 August 1995; accepted in final form 4 January 1996.
APS Manuscript Number F263-5.
Article publication pending Am. J. Physiol. (Renal Fluid Electrolyte
Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 25 January 96