Residual urinary concentrating ability and AQP2 expression in a rat model for chronic renal failure

In chronic renal failure (CRF), a defect in urinary concentrating ability develops gradually as the renal failure progresses. Although several molecular mechanisms associated with renal urinary concentration are reported to be impaired in a rat model for renal failure, the mechanisms underlying residual urinary concentration ability in CRF remain to be elucidated.

Rats that underwent an 8-week recovery period after 5/6 nephrectomy were used as the model for CRF. Urinary concentration was induced by 24-hour water restriction. Plasma osmolality and arginine vasopressin (AVP) were measured from blood sampled by inserting a catheter into the femoral artery before and after the water restriction. AQP2 mRNA expression in the inner medulla was examined by competitive PCR and in situ hybridization, and protein expression, by Western blotting. Rats that underwent sham operation were used as control.

Water restriction significantly reduced urine volume and increased urine osmolality in CRF rats, although such changes were much less than those in sham-operated rats. Plasma AVP was elevated at the basal condition, and further elevation was noted after water restriction. AQP2 mRNA signals were significantly intensified by water restriction even in CRF rats, although the increase was limited as in the case of urine osmolality. Western blotting also showed a small but significant enhancement of protein signals in response to water restriction in CRF rats.

We noted a weak but significant response of AQP2 expression to dehydration in CRF rats. This response in the collecting duct may be one of the factors contributing to residual urinary concentrating ability in CRF.