HYPOXIA-REOXYGENATION IMPAIRS NO-MEDIATED PULMONARYVASODILATION AND CAUSES LIPID PEROXIDATION IN ISOLATED RAT LUNGS. EDDAHIBI, Saadia, Bernadette RAFFESTIN, Yvan TAYARANI, Claudine CARVILLE, Serge ADNOT. D‚partement de physiologie et INSERM U 296, CHU Henri Mondor, 94010 Cr‚teil, France, D‚partement de physiologie, Universit‚ Ren‚ Descartes, H“pital Ambroise Par‚, 92100 Boulogne, France
APStracts 3:0072L, 1996.
To explore NO-mediated pulmonary vasodilation during oxidant-induced vascular injury, we examined the responses to both ionophore A23187 (an endothelium- dependent NO-mediated vasodilator) and exogenous NO in isolated rat lungs subjected to hypoxia-reoxygenation. After 30 min ventilation with 3% O 2 , reoxygenation with 21% (H/R 21%) or 95 % O2 (H/R 95%) caused an increase in malondialdehyde tissue levels as compared to respective values in lungs continuously ventilated with 21% or 95% O 2 (13.6 +/- 1.2 vs 11.8 +/- 0.8, p<0.05 and 15.2 +/- 1.3 vs 12.4+/- 0.9 [mu]mol/mg protein, p < 0.05), an increase in wet-to-dry lung weight ratio (7.2 +/- 0.3 vs 5.2 +/- 0.3, p < 0.05, and 9.1 +/- 0.6 vs,p < 0.01) but no change in superoxide dismutase and gluthathion peroxidase activities. Vasodilation to A23187 (10 -9 to 10 -7 M), studied under conditions of increased tone by U46619, was attenuated after H/R 21% and abolished after H/R 95%. The vasodilator-response curve to NO (10 -9 - 10 -7 M) was shifted to the right with a more pronouced effect after H/R 95% than after H/R 21%. Pretreatment before reoxygenation with the antioxidants superoxide dismutase (150 U/ml) and catalase (120 U/ml) prevented lipid peroxidation, edema formation and impairment of A23187 or NO-mediated vasodilation. Administration of the antioxidants after reoxygenation restored vasodilation to NO but not that to ionophore A23187. Similar results were obtained using the oxygen free radicals generator pyrogallol (3 x 10 -5 M). These data suggest that lung hypoxia-reoxygenation induces the generation of oxygen-derived reactive species, with subsequent impairment of NO formation as well as direct inactivation of NO. In lungs obtained from chronically hypoxic rats, but studied under conditions of normoxic ventilation, vasodilation to A23187 was abolished but vasodilation to NO remained unchanged. Generation of oxygen-derived reactive species does not account for the decreased endothelial NO-mediated pulmonary vasodilation in chronically hypoxic rats. 

Received 20 June 1995; accepted in final form 8 May 1996.
APS Manuscript Number L194-5.
Article publication pending Am. J. Physiol. (Lung Cell. & Mol. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 28 May 96