Reactive Oxygen Metabolites Produce Pulmonary Vasoconstriction in Young Pigs

Abstract

ABSTRACT. 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 (cyclooxygenase 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. (Pediatr Res 29: 543-547, 1991) Abbreviations Hx, hypoxanthine PVR, pulmonary vascular resistance XO, xanthine oxidase Pao2, arterial oxygen tensionThe complex mechanisms governing the pulmonary circulation in the perinatal period have recently been given extensive consideration in several review articles (1-3). Oxygen-derived free radicals play an important role in experimentally induced hypoxic-reoxygenation injury (4, 5), and may be responsible for both hypoxic and hyperoxic aspects of pulmonary damage (6-

Effects of N-Acetylcysteine on Pulmonary Macrophage Activity after Intestinal Ischemia and Reperfusion in Rats / with Invited Commentaries

“…Intestinal I/R leads to pulmonary vasomotor dysfunction, with an imbalance of vascular smooth muscle contraction and relaxation [33], and pulmonary upregulation of the potent vasoconstrictor thromboxane A 2 , TXA 2 [34]. It has been suggested that oxygen radicals play a role in these events [35, 36], a finding that is supported by the fact that NAC pretreatment in patients undergoing operation for abdominal aortic aneurysm prevented against the increase in plasma lipid peroxide levels, thromboxane, and prostacyclin levels seen in patients not receiving pretreatment [32]. Based on these reports and our findings on the effectiveness of treatment with NAC, it is thus possible that reactive oxygen species are involved in mediating the decrease in pulmonary blood content seen after intestinal I/R.…”

Role of Superoxide Anion on Basal and Stimulated Nitric Oxide Activity in Neonatal Piglet Pulmonary Vessels

“…The pulmonary vessels are continually exposed to free radicals and reactive oxygen species originating from inspired air or inflammatory cells, and pulmonary vascular tone is dramatically altered by reactive oxygen species such as O 2 ⅐Ϫ (3,4). At birth, the newborn encounters a much more oxygen-enriched world than the relatively hypoxic fetus.…”

Sodium Nitroprusside Prevents Oxygen-Free-Radical-Induced Pulmonary Vasoconstriction in Newborn Piglets

“…Perfusion of XO (or with hypoxanthine) to isolated rat lungs increased pulmonary artery pressure (PAP) and vascular resistance (PVR) [8]. Similarly, previous in vivo studies from our group demonstrated that infusion of XO induced a significant pulmonary vasoconstriction in young pigs (8 weeks old) [7,9]. Its effects on the neonatal pulmonary hemodynamics, however, have not been investigated.…”

“…Tate et al [5] and Sanderud et al [7,10] reported that the activation of cyclooxygenase subsequent with releasing thromboxane might account for its mechanisms.…”

“…When hypoxanthine is oxi-dized to uric acid by XO, the superoxide free radicals are generated according to the following equation: Hypoxanthine Superoxide anion and hydrogen peroxide can further react with transitional metal ions and generate toxic hydroxyl radicals. Oxygen free radicals induce vascular injury [4][5][6][7]. Perfusion of XO (or with hypoxanthine) to isolated rat lungs increased pulmonary artery pressure (PAP) and vascular resistance (PVR) [8].…”