Role of AQP1 in endotoxemia-induced acute kidney injury.
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.
Wang
Weidong
W
Department of Medicine, Division of Renal Diseases and Hypertension, Univ. of Colorado Health Sciences Center, 4200 East 9Ave., Box B173, Denver, CO 80262, USA.
Li
Chunling
C
Summer
Sandra N
SN
Falk
Sandor
S
Wang
Wei
W
Ljubanovic
Danica
D
Schrier
Robert W
RW
D000208:Acute Disease; D000818:Animals; D051398:Aquaporin 1 / Q000235:genetics* / Q000378:metabolism*; D001794:Blood Pressure; D004326:Drinking / Q000502:physiology; D019446:Endotoxemia / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D005919:Glomerular Filtration Rate; D007668:Kidney / Q000473:pathology / Q000502:physiology; D007674:Kidney Diseases / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D011141:Polyuria / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D012079:Renal Circulation; D014867:Water / Q000378:metabolism
C496021:Aqp1 protein, mouse; D008070:Lipopolysaccharides; D014867:Water; D051398:Aquaporin 1