Ischaemia--reperfusion injury in the rat is modulated by superoxide generation and leads to an augmentation of the hypoxic pulmonary vascular response.
1. The effects of the scavengers of reactive oxygen species superoxide dismutase and catalase, the iron chelator desferrioxamine and the nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester and saline (control vehicle) on hypoxic pulmonary vasoconstriction, a measure of albumin flux and an index of lipid peroxidation (palmitic:linoleic acid ratio) were investigated after ischaemia-reperfusion in an isolated, blood-perfused rat lung model. 2. Lungs treated immediately before reperfusion with catalase (5,000 units), desferrioxamine (2 mg/kg), NG-nitro-L-arginine methyl ester (5 mmol/l) or saline showed a significant augmentation in pre-ischaemia-reperfusion hypoxic pulmonary vasoconstriction (57.7 +/- 6.0%, 82.7 +/- 28.8%, 95.2 +/- 36.6% and 45.95 +/- 10.53% respectively), an increase in albumin flux (0.35 +/- 0.04, 0.31 +/- 0.06, 0.29 +/- 0.04 and 0.33 +/- 0.02) and an increase in pre-ischaemia-reperfusion palmitic:linoleic acid ratio (0.64 +/- 0.08, 0.51 +/- 0.19, 0.5 +/- 0.04 and 0.17 +/- 0.07). Superoxide dismutase (2,750 i.u.) administered immediately before reperfusion prevented completely the changes in hypoxic pulmonary vasoconstriction (-0.3 +/- 5.4%), albumin flux (0.09 +/- 0.11) and palmitic:linoleic acid ratio (-0.06 +/- 0.12). In control lungs (2h of continuous perfusion), superoxide dismutase, catalase, desferrioxamine and saline did not affect hypoxic pulmonary vasoconstriction (5.5 +/- 4.9%, 1.0 +/- 3.1%, -5.1 +/- 1.8% and 3.0 +/- 6.6%). However, NG-nitro-L-arginine methyl ester significantly augmented hypoxic pulmonary vasoconstriction (275.1 +/- 39.3%). There was no effect of superoxide dismutase, catalase, desferrioxamine, NG-nitro-L-arginine methyl ester or saline in control lungs on albumin flux (0.10 +/- 0.04, 0.11 +/- 0.01, 0.1 +/- 0.01, 0.12 +/- 0.01 and 0.11 +/- 0.01 respectively) or palmitic:linoleic acid ratio (-0.08 +/- 0.08, 0.73 +/- 0.76, -0.03 +/- 0.12, 0.01 +/- 0.17 and 0.00 +/- 0.0 respectively). 3. We conclude that superoxide dismutase attenuates ischaemia-reperfusion-induced increases in albumin flux and hypoxic pulmonary vasoconstriction, and prevents consumption of linoleic acid in the isolated, blood-perfused rat lung.
Messent
M
M
Unit of Critical Care, National Heart and Lung Institute, London, UK.
Griffiths
M J
MJ
Quinlan
G J
GJ
Gutteridge
J M
JM
Evans
T W
TW
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D002374:Catalase / Q000494:pharmacology; D003676:Deferoxamine / Q000494:pharmacology; D007511:Ischemia / Q000378:metabolism*; D008042:Linolenic Acids / Q000378:metabolism; D008168:Lung / Q000098:blood supply* / Q000378:metabolism; D008297:Male; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000037:antagonists & inhibitors; D010088:Oxidoreductases / Q000494:pharmacology; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D015427:Reperfusion Injury / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects*
D008042:Linolenic Acids; D017382:Reactive Oxygen Species; D009569:Nitric Oxide; D001120:Arginine; D010088:Oxidoreductases; D002374:Catalase; D013482:Superoxide Dismutase; D003676:Deferoxamine; D019331:NG-Nitroarginine Methyl Ester