The normal physiology of the lung may be compromised by conditions which result in lung injury. Normal functions include adequate gas exchange and metabolism of circulating vasoactive substances. Alterations in these activities can have serious consequences in regard to systemic physiology. Hypoxemia and chronic or acute changes in blood pressure may result from damage to lung tissue. Altered and/or interrupted ventilation and perfusion, hypoxia, reduced temperature, and exposure to high oxygen tensions and gaseous anesthetics are known to reduce the metabolism of circulating vasoactive substances by the lung. Little is known regarding the time course of onset or extent of damage, or of factors which may accelerate or inhibit its reversal. This research program will investigate the development and reversal of damage to the lung, especially to the pulmonary endothelium, resulting from these and similar interventions. The activity of angiotensin converting enzyme in the cleavage of angiotensin I to angiotensin II and the uptake and inactivation of 5-hydroxytryptamine and prostaglandin E1 will be monitored as indices of pulmonary endothelial cell function in perfused lungs, cultured endothelial cells and subcellular fractions. Metabolic parameters of the lung in general will also be monitored during lung injury. In addition, these studies will include investigation of the mechanism of the observed effects in order to localize the alterations to specific steps in the membrane associated processes and more clearly define conditions required for prevention and/or rapid reversal of damage.
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| Catravas, J D; Watkins, C A (1985) Plasmalemmal metabolic activities in cultured calf pulmonary arterial endothelial cells. Res Commun Chem Pathol Pharmacol 50:163-79 |
