Article

Inhibition of nitric oxide synthase reduces renal ischemia/reperfusion injury.

Department of Surgery, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106, USA.
Journal of Surgical Research (impact factor: 2.25). 01/2006; 129(2):236-41. DOI:10.1016/j.jss.2005.06.019 pp.236-41
Source: PubMed

ABSTRACT The role of nitric oxide (NO) production because of inducible nitric oxide synthase (iNOS) in the pathogenesis of renal ischemia/reperfusion (I/R) injury is unclear. In this study the roles of both iNOS and NO were characterized in a rat model of renal I/R injury. In addition, the effect of iNOS inhibition on renal function was evaluated.
Sprague-Dawley rats underwent 45 min of left renal ischemia and contralateral nephrectomy followed by various periods of reperfusion and renal function analysis [plasma creatinine, fractional excretion of sodium (FENa), creatinine clearance (CrCl), and measurement of plasma and urine NO levels]. In addition, the effect of treatment with 1400W, a highly selective iNOS inhibitor, was evaluated.
Renal dysfunction peaked at 48 h after reperfusion and immunohistochemistry studies revealed iNOS expression in the vasculature (3 h) and renal tubules (48 h) after reperfusion. Renal function improved significantly in treated animals compared to controls [creatinine of 1.1 v. 1.9 mg/dl (P < 0.05) and CrCl of 0.54 v. 0.31 ml/min (P < 0.05), respectively]. In addition, FENa was decreased by 50%, plasma NO levels were significantly lower (32.7 v. 45.7 micromol/L, P < 0.01), and deposition of nitrotyosine in the tubules of treated rats was less than in control animals.
These data support the hypothesis that iNOS and NO are involved in the pathogenesis of renal I/R injury and suggests that use of iNOS inhibitors may be a valuable therapeutic strategy clinical situations where renal I/R may be prevalent.

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Keywords

control animals
 
controls [creatinine
 
creatinine clearance
 
data support
 
fractional excretion
 
immunohistochemistry studies
 
inducible nitric oxide synthase
 
iNOS expression
 
iNOS inhibition
 
iNOS inhibitors
 
rat model
 
Renal function
 
renal function analysis [plasma creatinine
 
renal I/R
 
renal I/R injury
 
renal ischemia/reperfusion
 
selective iNOS inhibitor
 
Sprague-Dawley rats
 
valuable therapeutic strategy clinical situations
 
various periods
 

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