ISCHEMIA-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 nit ric oxide synthase inhibitor N-G-nitro-L-arginine methyl ester and sal ine (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 isola ted, blood-perfused rat lung model. 2. Lungs treated immediately befor e reperfusion with catalase (5000 units), desferrioxamine (2 mg/kg), N -G-nitro-L-arginine methyl ester (5 mmol/l) or saline showed a signifi cant augmentation in pre-ischaemia-reperfusion hypoxic pulmonary vasoc onstriction (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, 0.5 1 +/- 0.19 0.5 +/- 0.04 and 0.17 +/- 0.07), Superoxide dismutase (2750 i.u.) administered immediately before reperfusion prevented completel y the changes in hypoxic pulmonary vasoconstriction (-0.3 +/- 5.4%), a lbumin flux (0.09 +/- 0.11) and palmitic:linoleic acid ratio (-0.06 +/ - 0.12). In control lungs (2 h of continuous perfusion), superoxide di smutase, catalase, desferrioxamine and saline did not affect hypoxic p ulmonary vasoconstriction (5.5 +/- 4.9%, 1.0 +/- 3.1%, -5.1 +/- 1.8% a nd 3.0 +/- 6.6%). However, N-G-nitro-L-arginine methyl ester significa ntly augmented hypoxic pulmonary vasoconstriction (275.1 +/- 39.3%), T here was no effect of superoxide dismutase, catalase, desferrioxamine, N-G-nitro-L-arginine methyl ester or saline in control lungs on album in 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 isc haemia-reperfusion-induced increases in albumin flux and hypoxic pulmo nary vasoconstriction, and prevents consumption of linoleic acid in th e isolated, blood-perfused rat lung.