Fasting downregulates renal water channel AQP2 and causes polyuria.

Starvation causes impairment in the urinary concentrating ability. The mechanism of this defect, however, remains unknown. We tested the possibility that food deprivation might affect the expression and activity of aquaporins (AQP1, 2), thereby impairing renal water reabsorption in the kidney. Rats fasted for 24 h exhibited severe polyuria (urine volume increased from 11 before fasting to 29 ml/24 h after fasting, P < 0.0001) along with failure to concentrate their urine (urine osmolality decreased from 1,485 before fasting to 495 mosmol/kgH(2)O after fasting, P < 0.0001). Refeeding for 24 h returned the urinary concentrating ability back to normal. Northern hybridization and immunoblot analysis demonstrated that fasting was associated with a decrease in AQP2 protein (-80%, P </= 0.002) and mRNA levels (-69%, P </= 0.003) in the outer medulla. In the cortex, fasting decreased AQP2 protein abundance by 60% (P </= 0.004) but did not alter its mRNA expression. During the recovery phase, AQP2 expression returned to normal level in both tissues. In the inner medulla, the expression of AQP2 was not altered in fasting, but was increased significantly at both protein ( +/- 92%) and mRNA ( +/- 43%) levels during the recovery from fasting. The proximal nephron water channel (AQP1) was not affected in response to fasting or recovery from fasting. We conclude that 1) fasting impairs the urinary concentrating ability in rats, and 2) the renal water-handling defect in fasting results specifically from the downregulation of AQP2 in the cortical and outer medullary collecting duct.