The primary objective of this proposed study is to quantitate and correlate the simultaneous physiological, histological, and ultrastructural changes that occur in the pulmonary vasculature during progressive and regressive hypoxic pulmonary hypertension. Rats will be exposed to a simulated high altitude of 18,000 ft in a hypobaric chamber, for six weeks, followed by a six week recovery period at 5,000 ft. Altitude-exposed rats and paired control rats will be studied frequently during the first two weeks, then at weekly intervals. Physiological measurements will include determination of the pulmonary pressor responses to acute hypoxia and a number of vasoactive agents in the isolated perfused lung preparation. These measures of pulmonary vascular reactivity will be correlated with histological (medial smooth muscle thickness of small pulmonary arteries, number of thick-walled peripheral lung vessels, and density and distribution of lung mast cells) and ultrastructural (subcellular components and smooth muscle and cardiac muscle cellular characteristics in arteries and veins) changes induced by the simulated high altitude exposure. The secondary objective is to assess the variability in these responses caused by the severity of the altitude exposure, age of the animals, and sex of the animals. In addition, the role of the sympathetic nervous system will be assessed by chemical sympathectomy of the rats with 6-hydroxydopamine prior to and during the altitude exposure. The information obtained from the proposed experiments will improve our understanding of the normal pulmonary circulation and will help to elucidate the anatomical and ultrastructural mechanisms involved in the genesis, development, and maintenance of pulmonary hypertension.