Attenuation of reperfusion injury by renal ischaemic preconditioning: the role of nitric oxide

OBJECTIVE: To determine the effect on nitric oxide (NO) release and renal NO synthase (endothelial, eNOS and inducible, iNOS) activity of renal ischaemia-reperfusion (I/R) in vivo in an animal model, and to examine the possible involvement of NO in ischaemic preconditioning (IP) of the kidney. MATERIALS AND METHODS: In a right-nephrectomized rat model, 42 animals were randomized in four groups: controls; IP-only (4 min of ischaemia followed by 11 min of reperfusion, total of four cycles); renal warm ischaemia (45 min) and 6 h reperfusion; ischaemia (45 min) preceded by IP pretreatment. Serum NO metabolites were assayed 2 and 6 h after ischaemia or the control equivalent. NOS expression in the kidney was detected immuno-histochemically, and damage assessed morphologically in sections stained with haematoxylin and eosin. Kidney function was assessed by the levels of serum creatinine, urea and electrolytes. RESULTS: Compared with before ischaemia, the concentration of serum NO metabolites at 6 h was increased in the IP-only animals (P = 0. 016) and in the IP + I/R group (P = 0.002). There was greater eNOS expression in the IP-only group (P = 0.009) and in the IP + I/R group than in controls (P = 0.050). iNOS expression was greater in the IP-only animals than in the control group (P = 0.050). Histological assessment showed less evidence of cellular damage in IP + I/R animals than in the I/R-alone group (P = 0.020). Serum creatinine level was not significantly different between the IP-only group and the control. There were no differences after 2 h of reperfusion. CONCLUSION: Ischaemic preconditioning has a protective effect on renal structure and function, which may be produced by increased NO release arising from increased NOS expression by 6 h after reperfusion.