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 ischaem ia-reperfusion (I/R) in vivo in an animal model, and to examine the possibl e 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; IF-only (4 min of ischaemia followed b y 11 min of reperfusion, total of four cycles); renal warm ischaemia (45 mi n) and 6 h reperfusion; ischaemia (45 min) preceded by IP pretreatment. Ser um NO metabolites were assayed 2 and 6 h after ischaemia or the control equ ivalent. NOS expression in the kidney was detected immuno-histochemically, and damage assessed morphologically in sections stained with haematoxylin a nd eosin. Kidney function was assessed by the levels of serum creatinine, u rea and electrolytes. Results Compared with before ischaemia, the concentration of serum NO metab olites at 6 h was increased in the IP-only animals (P=0.016) and in the IPI/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 express ion 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 n ot 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 struc ture and function, which may be produced by increased NO release arising fr om increased NOS expression by 6 h after reperfusion.