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.


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.


CONCLUSIONS
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.
Jefayri
M K
MK
Division of Surgery, Anaesthetics and Intensive Care, Imperial College School of Medicine, Hammersmith Hospital, London, UK.
Grace
P A
PA
Mathie
R T
RT
D000818:Animals; D005260:Female; D007150:Immunohistochemistry; D019194:Ischemic Preconditioning / Q000379:methods*; D007668:Kidney / Q000098:blood supply* / Q000378:metabolism; D007672:Kidney Cortex / Q000098:blood supply / Q000378:metabolism / Q000473:pathology; D017078:Laser-Doppler Flowmetry; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000517:prevention & control*
D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496318:Nos2 protein, rat; C496316:Nos3 protein, rat