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. Materi...

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Veröffentlicht in:BJU international 2000-06, Vol.85 (9), p.1007-1013
Hauptverfasser: Jefayri, M.K., Grace, P.A., Mathie, R.T.
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Sprache:eng
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Zusammenfassung: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.
ISSN:1464-4096
1464-410X
DOI:10.1046/j.1464-410x.2000.00678.x