SUPEROXIDE RADICAL AND PULMONARY CIRCULATION

A. Tuncay DEMIRYÜREK*°

*Gazi University, Faculty of Pharmacy, Department of Pharmacology, 06330 Etiler, Ankara, TURKEY.
°Corresponding Author

Summary:
Pulmonary endothelial cells, smooth muscle cells and lung macrophages have all been shown to generate superoxide radicals, both under basal and stimulated conditions. Many oxidase enzymes are capable of forming superoxide radical; the best characterised are xanthine oxidase, cylooxygenase, lipoxygenase, nitric oxide synthase, NADPH oxidase and NADH oxidase. The superoxide radicals reacts with NO released from the endothelium, thus antagonising endothelium-dependent relaxation and promoting contraction in pulmonary artery rings. Additionally, the superoxide radical can cause contraction of the pulmonary artery through the participation of protein kinase C but not calcium. The pulmonary vasoconstrictor effect of xanthine / xanthine oxidase in anaesthetized animals or in perfused lungs is also associated with the formation of thromboxanes, leukotrienes, and prostaglnadings. SOD specifically destroys the superoxide radical by conversion to H2O2 , so preventing the production of hydroxyl radical and peroxynitrite. Metallothionein, a low molecular weight metalloprotein, is also able to serve as a scavenger of superoxide radical generated by xanthine/xanthine oxidase. Hypoxia reduces spontaneous superoxide radical formation, but after prolonged hypoxia, xanthine oxidase activity can be upregulated. Hyperoxia damages the epithelial cells by of the alveoli and the pulmonary vascular endothelial cells by generation of reactive oxygen species. The superoxide radical may also play a significant role in pulmonary diseases such as acute respiratory distress syndrome, ischaemia-reperfusion injury, and lung transplantation. The superoxide radical decays rapidly to hydrogen peroxide and peroxynitrite, which have potent actions and may be the active forms for some of the effects of the superoxide radical described in vivo. The best working current hypothesis is to assume that in healthy cells the optimal balance exists between superoxide radical generation and superoxide radical scavenging. If this balance is lost under pathological conditions, the best therapeutic goal would be the restoration of the optimal balance.

Key words:
Superoxide radical, SOD, Pulmonary circulation, Pulmonary diseases.