Biphasic role for nitric oxide in experimental renal warm ischaemia-reperfusion injury.
BACKGROUND
Whilst nitric oxide has a clearly defined role in renal haemostasis, debate continues over its pathophysiology. This study investigated the function of nitric oxide in a model of renal warm ischaemia-reperfusion injury.


METHODS
Rats underwent bilateral renal warm ischaemia (45 min) after pretreatment with nitric oxide donors, nitric oxide synthase (NOS) inhibitors or saline (control). Following reperfusion (20 min) a unilateral nephrectomy was performed to measure renal nitric oxide (as nitroxides) and oxidative DNA and protein damage. Renal function was measured on days 2 and 7 before terminal nephrectomy for analysis and morphology.


RESULTS
The increase in renal nitric oxide level seen early in reperfusion (20 min) (P < 0.01) was prevented by inhibition of constitutive (cNOS) but not inducible (iNOS) NOS. The increase in oxidative damage (P < 0.01) was exacerbated by nitric oxide donors (P < 0.01) but ameliorated by NOS inhibition (P < 0.01). Control nitric oxide remained increased through to day 7 (P < 0.01) but was reduced by nitric oxide donors and cNOS inhibitors (P < 0.05). Oxidative damage returned towards normal in the control group, whereas both DNA and protein damage persisted following NOS inhibition (P < 0.01).


CONCLUSIONS
Inhibition of the postischaemic increase in the level of nitric oxide was associated with an early decrease in, but eventual exacerbation of, oxidative damage. This suggests the prolonged increase in renal nitric oxide concentration was cytoprotective overall.
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University Department of Surgery, Leicester General Hospital, Leicester LE5 4PW, UK.
Furness
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Nicholson
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D000818:Animals; D004249:DNA Damage; D005919:Glomerular Filtration Rate / Q000502:physiology; D007668:Kidney / Q000098:blood supply* / Q000378:metabolism; D008297:Male; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II; D018384:Oxidative Stress; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000209:etiology* / Q000378:metabolism
D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II; C496322:Nos1 protein, rat; C496318:Nos2 protein, rat