Reduced abundance of aquaporins in rats with bilateral ischemia-induced acute renal failure: prevention by alpha-MSH

We examined the effect of temporary renal ischemia (30 min or 60 min) and r eperfusion (1 day or 5 days) on the expression of renal aquaporins (AQPs) a nd urinary concentration in rats with bilateral ischemia-induced acute rena l failure (ARF). Next, we tested whether reducing ischemia/reperfusion (I/R ) injury by treatment with or-melanocyte stimulating hormone (alpha-MSH) af fects the expression of AQPs and urine output. Rats with ARF showed signifi cant renal insufficiency, and urinary concentration was markedly impaired. In rats with mild ischemic injury (30 min), urine output increased signific antly to a maximum at 48 h, and then nearly normalized within 5 days. Consi stent with this, semiquantitative immunoblotting revealed that kidney AQP1 and AQP2 abundance was significantly decreased after 24 h to 30 +/- 5% and 40 +/- 11% (n = 8) of controls (n = 9), respectively (P < 0.05). Five days after ischemia, AQP2 abundance was not significantly decreased and urine ou tput was normalized. In contrast, severe ischemic injury (60 min) resulted in a marked reduction in urine output at 24 h, despite a significant decrea se in urine osmolality and solute-free water reabsorption, (TH2O)-H-c. AQP1 and AQP2 abundance was markedly decreased to 51 +/- 5% and 31 +/- 9% (n = 10) of controls (n = 8) at 24 h (P ( 0.05). After 5 days, the rats develope d gradually severe polyuria and had very low AQP2 and AQP1 levels [11 +/- 4 % and 6 +/- 2% (n = 5) of controls (n = 8), respectively; P < 0.05]. A simi lar reduction was observed for AQP3. The reduction in AQP expression in the proximal tubule and inner medullary collecting duct was confirmed by immun ocytochemistry. Next, we found that intravenous (alpha-MSH treatment of rat s with ARF significantly reduced the ischemia-induced downregulation of ren al AQPs and reduced the polyuria. In conclusion, the I/R injury is associat ed with markedly reduced expression of the collecting duct and proximal tub ule AQPs, in association with an impairment of urinary concentration. Moreo ver, alpha-MSH treatment significantly prevented the reduction in expressio n of AQPs and renal functional defects. Thus decreased AQP expression is li kely to contribute to the impairment in urinary concentration in the postis chemic period.