Nitric oxide generation is increased in experimental renal warm ischaemia-reperfusion injury.
BACKGROUND
Nitric oxide has a clearly defined place in normal renal homoeostasis while there is a continuing debate as to its role under pathophysiological conditions. This study investigated the role of nitric oxide in a model of renal warm ischaemia-reperfusion injury.


METHODS
Groups of rats underwent bilateral renal warm ischaemia (for 15-60 min) followed by reperfusion (20 or 80 min) before unilateral nephrectomy for measurement of renal nitric oxide (as nitroxides) and oxidative damage. Renal function was measured on days 2 and 7 before killing and nephrectomy. A further group received the nitric oxide synthase inhibitor N(G)-nitro L-arginine methyl ester (L-NAME; 50 mg per kg body-weight) before induction of warm ischaemia.


RESULTS
In early reperfusion there was a correlation between the duration of warm ischaemia (15-45 min) and renal nitrate (r2=0.97) which increased from a mean(s.e.m.) baseline value of 95(5.9) to 208(17.3) nmol per mg protein following 45 min of warm ischaemia. Levels were further raised at 80 min and maintained through to day 7 (241(12.5) nmol per mg protein in 45-min group). This rise was attenuated by L-NAME (P< 0.01) as was the early rise in oxidative damage seen otherwise. By day 7, however, oxidative damage was increased (all P< or = 0.01).


CONCLUSIONS
Renal nitric oxide increased early in recoverable warm ischaemia-reperfusion injury and remained raised to day 7. Nitric oxide synthase inhibition ameliorated early but exacerbated late damage suggesting that the early burst of nitric oxide is cytotoxic but that overall nitric oxide may exert a cytoprotective effect.
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University Department of Surgery, Leicester General Hospital, UK.
Furness
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Nicholson
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ML
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000818:Animals; D004249:DNA Damage; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000378:metabolism; D005919:Glomerular Filtration Rate / Q000502:physiology; D006358:Hot Temperature; D007511:Ischemia / Q000378:metabolism*; D007668:Kidney / Q000098:blood supply*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000378:metabolism*
D009569:Nitric Oxide; D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine; D019331:NG-Nitroarginine Methyl Ester