Reactive oxygen metabolites produce pulmonary vasoconstriction in young pigs.
Reactive oxygen metabolites appear to modulate pulmonary vascular changes. To study the effects of free radical formation in vivo, we investigated five groups of young pigs by recording hemodynamic changes after xanthine oxidase infusion alone and after pretreatment with hypoxanthine or possible blocking agents. The pulmonary vascular pressure increased rapidly in the groups without inhibition reaching maximum levels 25 min after the start of the experiment. The pulmonary artery blood flow declined toward minimum values at the same time. Compared to baseline levels, the calculated vascular lung resistance increased by 300% when the pigs were pretreated with hypoxanthine, and by 150% when xanthine oxidase was given alone. These findings suggest enhanced pulmonary vasoconstriction as a result of high initial hypoxanthine levels probably capable of forming larger quantities of oxygen radicals. The vascular reaction was attenuated when the pigs were pretreated with indomethacin (cyclo-oxygenase inhibitor) or allopurinol (xanthine oxidase inhibitor). Furthermore, the presence of catalase (hydrogen peroxide scavenger) reduced the pulmonary vasoconstriction significantly. We observed less decline in arterial oxygen tension and oxygen saturation when the animals had been pretreated with inhibitory agents, compared to the blood gas changes found in the xanthine oxidase group. The systemic pressure recordings in the carotid artery remained at baseline levels in all groups. We conclude that oxygen radicals formed by the hypoxanthine-xanthine oxidase system produce severe pulmonary vascular constriction in young pigs.
Sanderud
J
J
Department of Pediatrics, University of Oslo, Rikshospitalet, Norway.
Norstein
J
J
Saugstad
O D
OD
D000493:Allopurinol / Q000494:pharmacology; D000818:Animals; D002374:Catalase / Q000494:pharmacology; D005260:Female; D005609:Free Radicals; D019271:Hypoxanthine; D007042:Hypoxanthines / Q000378:metabolism / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D010100:Oxygen / Q000378:metabolism*; D011652:Pulmonary Circulation / Q000187:drug effects / Q000502:physiology*; D013552:Swine; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*; D014969:Xanthine Oxidase / Q000378:metabolism / Q000494:pharmacology
D005609:Free Radicals; D007042:Hypoxanthines; D019271:Hypoxanthine; D000493:Allopurinol; D002374:Catalase; D014969:Xanthine Oxidase; D010100:Oxygen; D007213:Indomethacin