The effect of
endotoxemia (
lipopolysaccharide, 2.5 mg/kg ip) was investigated in
aquaporin (AQP) 1 knockout (KO) compared with wild-type (WT) mice. At baseline, KO mice exhibited higher water intake (WI) and urine output (UO). After
endotoxemia, WI and UO remained higher in the KO than WT mice, and urine osmolality was lower. The higher serum osmolality in AQP1-KO mice during
endotoxemia was associated with higher AQP2 (133 +/- 8 vs. 100 +/- 3%, P < 0.01), AQP3 (140 +/- 8 vs. 100 +/- 4%, P < 0.001) and Na(+)-K(+)-2Cl(-) cotransporter type 2 (NKCC2; 152 +/- 14 vs. 100 +/- 15%, P < 0.05) expression than that in WT mice. These responses during
endotoxemia in the AQP1-KO mice compared with WT were associated with lower glomerular filtration rate (GFR) (69 +/- 8 vs. 96 +/- 8 ml/min, P < 0.05) and renal blood flow (0.77 +/- 0.1 vs. 1.01 +/- 0.1 ml/min, P < 0.01). Urinary
sodium excretion and fractional
sodium excretion were higher in KO compared with WT mice in
endotoxemia and were accompanied by more severe tubular injury. With water repletion and comparable serum osmolalities, GFR was still lower in KO (57 +/- 13 vs. 120 +/- 6 ml/min, P < 0.01) compared with WT during
endotoxemia. The abundance of AQP2 and
AQP3 protein in KO mice was not different from WT mice; however, NKCC2,
Na(+)/H(+) exchanger type 3, and fractional
sodium excretion remained higher in KO compared with WT. Thus the
polyuria in AQP1-KO mice does not protect against
endotoxemia-induced
acute kidney injury but rather absence of AQP1 predisposed to enhanced endotoximic renal injury.