Toxic oxygen metabolites induce vasoconstriction and bronchoconstriction in isolated, plasma-perfused rat lungs.
Effects of toxic oxygen metabolites (TOM) on the pulmonary vascular bed and airways were studied in isolated, plasma-perfused rat lungs. TOM were generated by xanthine oxidase (XO) (0.1 or 0.25 unit.ml-1) and hypoxanthine (HX) (1 mol.l-1). In vitro measurements by chemiluminescence indicated that the major oxygen metabolite generated by XO and HX was H2O2. Measurements of PO2 in the perfusate as an indicator of O2-consumption suggested that production of TOM by XO and HX was finished within 30 min. XO and HX induced an early dose-dependent bronchoconstriction and a late increase in transpulmonary pressure (Ptp). Pulmonary arterial pressure (Ppa) increased gradually and levelled off within 30 min with low-dose XO, but not with high-dose XO. As judged by weight increase of the lungs, interstitial edema occurred regularly. Allopurinol, an inhibitor of XO, blocked the lung responses caused by XO and HX. Catalase attenuated all lung responses induced by XO and HX, while superoxide dismutase had no effect. The hydroxyl radical scavenger dimethylsulfoxide abolished the increase in Ptp and attenuated the increase in Ppa, but did not consistently protect the lungs from edema development. This study shows that TOM induce vasoconstriction, bronchoconstriction and lung edema in plasma-perfused rat lungs, mainly due to generation of H2O2 and the hydroxyl radical.
Kjaeve
J
J
Department of Anesthesiology and Surgery, University of Tromsø, Norway.
Vaage
J
J
Bjertnaes
L
L
D000818:Animals; D016084:Bronchoconstriction; D005609:Free Radicals; D019271:Hypoxanthine; D007042:Hypoxanthines / Q000378:metabolism; D066298:In Vitro Techniques; D008168:Lung / Q000098:blood supply*; D008297:Male; D010100:Oxygen / Q000097:blood* / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D014661:Vasoconstriction; D014969:Xanthine Oxidase / Q000378:metabolism
D005609:Free Radicals; D007042:Hypoxanthines; D019271:Hypoxanthine; D014969:Xanthine Oxidase; D010100:Oxygen