Energetically active forms of oxygen may be exceedingly toxic to mammalian systems. The lungs are the initial site of entry for the gaseous forms of activated oxygen and may, in addition, produce activated oxygen by metabolism of chemicals delivered through the vasculature. Initial responses to these toxins may be biochemical defenses, damage to metabolic systems, alterations in pulmonary physiologic responses and whole organ hemodynamic changes. Each of these aspects of of the total pulmonary response to activated oxygen will be investigated. Models of energetically active oxygen are ozone, increased inspired oxygen (PI02), and paraquat (methyl viologen). Ozone and increased PI02 may be toxic individually and may also give rise to other forms of oxygen, e.g. superoxide anion (02-) and peroxide anion(02=). These same anion oxidants are known pulmonary metabolic products of paraquat. Biochemical studies will investigate oxygen sensitive responses in whole cell and intact organ preparations following in vitro and in vivo treatments. Direct (in vitro) and whole animal (in vivo) responses in pulmonary glucose metabolism, collagen metabolism, active chemical uptake, cytochrome function, and endothelial cell enzyme activity (angiotensin converting enzyme) will be examined. Furthermore, alterations in the oxygen dependency of each of these pulmonary systems will be determined. Oxidant effects on pulmonary smooth muscle preparations will elucidate changes in physiologic responses which may contribute directly to the oxidant lesion which is characteristically observed in the small airways. In a similar manner, oxidant damage may lead to alterations in vascular smooth muscle reactivity and could produce changes in pulmonary hemodynamics and gas exchange functions. Both pulmonary hemodynamics and respiratory function will be evaluated in isolated lungs and in intact animals. The combined information about these biochemical, physiological and functional pulmonary responses to activated oxygen will provide a firm basis for the prevention and treatment of oxidant lung damage.