Attenuation of renal ischemia-reperfusion injury in inducible nitric oxidesynthase knockout mice

Renal ischemia-reperfusion (IIR) injury was investigated in inducible nitri c oxide synthase (iNOS) knockout mice. After a 26-min bilateral renal pedic le clamp, serum creatinine concentrations tin mg/dl) in wild-type mice afte r a 24-h reperfusion were 0.25 +/- 0.03 in sham-operated controls and 2.3 /- 0.38 in ischemic mice (P < 0.01); after 48 h, concentrations (in mg/dl) were 0.25 +/- 0.03 in controls and 2.0 +/- 0.18 in ischemic mice (P < 0.01) . iNOS knockout mice demonstrated an attenuation of serum creatinine concen tration after renal I/R injury. Serum creatinine concentrations (mg/dl) aft er a 24-h reperfusion were 2.3 +/- 0.22 in wild-type ischemic and 1.21 +/- 0.25 in iNOS knockout ischemic mice (P < 0.05); after 48 h, concentrations were 2.0 +/- 0.18 in wild-type ischemic and 0.96 +/- 0.25 in iNOS knockout ischemic mice (P < 0.01). Histological scoring of acute tubular necrosis in iNOS knockout mice was decreased compared with that in wild-type controls (0.88 +/- 0.2 vs. 3.3 +/- 0.3, P < 0.05). iNOS protein in the renal cortex of wild-type mice subjected to renal I/R injury was undetectable up to 48 h . However, a strong upregulation of heat shock protein 72 expression was ob served in renal cortex of iNOS knockout mice under basal conditions. In con clusion, kidneys of iNOS knockout mice were protected against ischemic acut e renal failure. This protective effect may be related to a compensatory up regulation of heat shock protein 72.