The long-term objective of this application is to investigate whether age-related changes occur in pulmonary vascular reactivity and in pulmonary vascular endothelial cell function. We propose to use the isolated, perfused and ventilated lungs from ferrets of ages ranging from young adults to elderly adults to achieve the following specific aims: 1. We propose to quantify the alterations in the strength of hypoxic pulmonary vasoconstriction in an animal model of aging 2. We will examine the pulmonary vascular response to increasing levels of alveolar carbon dioxide in young and aged animals 3. We will examine the effects of aging on pulmonary vascular resistance and distensibility 4. We will investigate the pulmonary vascular reactivity to known physiological humoral agents 5. We will measure the production of prostaglandins by the lungs of young and aged animals 6. We will measure the uptake of serotonin, angiotensin II, and prostaglandin E1 by the lungs to assess if alterations in pulmonary endothelial cell function occur with aging. Isolated, perfused ferret lungs will be exposed to various levels of oxygen and carbon dioxide to determine the dose response curves to these gases. Alterations in vascular resistance and distensibility will be determined in the lungs of young and aged ferrets by the outflow/inflow occlusion technique. Dose response curves to sustonin, angiotensin II, prostaglandins and norepinephrine will be constructed in isolated lungs of ferrets of various ages. We will measure the production of prostaglandins by RIA and by a lung microsomal assay. We will assess the effects of aging on endothelial cell function by examining the extraction of vasoactive substances from the blood. Analysis of the results from these experiments may provide information on how the aging process affects pulmonary vascular reactivity and pulmonary vasular endothelial cell function. This will contribute to our understanding of the known decrement of pulmonary function in healthy elderly adults as well as to the treatment of those suffering from chronic obstructive lung disease.
