Biphasic role for nitric oxide in experimental renal warm ischaemia-reperfusion injury

Background: Whilst nitric oxide has a clearly defined role in renal haemost asis, debate continues over its pathophysiology. This study investigated th e function of nitric oxide in a model of renal warm ischaemia-reperfusion i njury. Methods: Rats underwent bilateral renal warm ischaemia (45 min) after pretr eatment 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 D NA and protein damage. Renal function was measured on days 2 and 7 before t erminal 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 inhibit ion (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). Conclusion: 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.