Reduced renal expression of AQP2, p-AQP2 and AQP3 in haemorrhagic shock-induced acute renal failure

Abstract

Background. The aims of this study were to investigate the changes in the expression levels of renal aquaporins (AQPS) in response to haemorrhagic shock (HS) in rats and whether a change in the expression of AQPs was associated with parallel changes in urinary concentration. Methods. HS was induced by withdrawal of blood through the femoral artery in rats. A mean arterial blood pressure (MAP) of 40 mmHg was maintained for 1 h before blood was reinfused, and rats were kept in metabolic cages for urine measurements. Two days after HS, we examined the abundance of AQPs in kidney by semiquantitative immunoblotting. Results. HS rats (n = 13) developed acute renal insufficiency (creatinine clearance was 5.5 ± 0.4 vs 6.9 ± 0.3 ml/min/kg in sham-operated rats, n = 13, P < 0.05) and decreased urine osmolality (888 ± 88 vs 1799 ± 110 mosmol/kg H2O, P < 0.05). Consistent with this, semiquantitative immunoblotting revealed that the abundance of AQP2, phosphorylated (Ser256) AQP2 (p-AQP2) and AQP3 in whole kidney was significantly decreased after 2 days to 33 ± 4, 41 ± 9 and 35 ± 14% of sham levels, respectively (P < 0.05). Also, the abundance of AQP2, p-AQP2 and AQP3 in inner medulla was markedly decreased to 36 ± 8, 39 ± 10 and 34 ± 16% of sham levels (P < 0.05). In contrast, the abundance of AQP1 was not significantly changed compared with sham levels. Conclusions. The expression of the collecting duct water channel AQP2, p-AQP2 and AQP3 was significantly downregulated after HS, which may play an important role in the impaired urinary concentrating ability in HS-induced acute renal failure.