2002 Global Researcher Conference Proceeding
April 26 - 28, 2002
| Conference: | 2002 Global Researcher Conference |
|---|---|
| Title: | Correction of age-related polyuria by dDAVP: Molecular involvement of aquaporins and urea transporters |
| Authors: | Combet-Jeancenel, Sophie; Corman, B.; Verbavatz, Jean-Marc; Trinh-Trang-Than, Marie-Marcel |
| Institutions: | Service de Biologie Cellulaire, Departement de Biologie Cellulaire et Moleculaire |
Aging is commonly associated with polyuria, involving lower urine osmolality, higher urine flow rate and higher water intake in both rodents and humans. In the WAG/Rij strain of rats, such a defect occurs with age, despite normal AVP plasma levels, V2 receptor mRNA, number of nephrons and single nephron filtration rate. In contrast, we have recently shown that aquaporin-2 (AQP2) expression selectively decreased by ~80% in the kidney inner medulla collecting duct (IMCD) of senescent, 30 months old female WAG/Rij rats, compared to adult (10 month-old) animals. This reduction of AQP2 expression was accompanied by a defect in AQP2-targetting to the apical region of IMCD cells. Inner medullary osmolality was also lower in the kidney of senescent rats, as was the expression of the AVP-regulated, UT-A1 urea transporter. In the present work, we examined whether dDAVP (a specific, V2 receptor agonist) administration was able to correct this age-related defect in urinary concentration and we studied the molecular mechanisms involved. Long-term dDAVP administration restored urine flow rate and urine osmolality of senescent rats to normal values. This improvement was accompanied by a normalization of AQP2 expression levels in the inner medulla and by improved targeting of AQP2. In addition, inner medullary urea concentration was increased by long-term dDAVP administration, along with the expression of UT-A1. In conclusion these results demonstrate that AQP2- and UT-mediated polyuria in senescent rats can be corrected by a higher level of V2 receptor stimulation.
As both rodents and humans age, they often have to urinate more frequently. This urine is generally more dilute than normal. They also tend to drink more water. This happens despite the fact that many of the factors required for normal urine concentration are in place. Verbavatz, et al., showed that in one breed of rats, the numbers of aquaporin-2 (AQP2) dramatically decreases in older rats. Added to this reduction was the fact that the remaining AQP2 often didn't make it to the cell membrane where it has to be if it is to perform its function. In addition, the older rats had less concentrated fluid in the section of their kidney called the inner medulla. They also had lower numbers of a protein that transports urea (UT-A1).
The researchers administered a compound (dDAVP) which stimulated vasopressin 2 receptors (V2R) to older rats over an extended period of time. This treatment returned the older rats' urine levels and urine concentrations to normal. It also returned AQP2 levels to normal, improved AQP2's ability to get to the cell membrane, increased inner medullary concentration and UT-A1. The researchers concluded that increasing V2R stimulation can correct excessive urination caused by low AQP2 and UT-A1 numbers in older rats.