Pulmonary, vascular responses in rats exposed to chronic hypobaric hypoxia at two different altitude levels.

High altitude hypoxia is known to cause pulmonary hypertension in humans. Altitudes of 5500 m and 4000 m above sea level are considered to be the upper limits for short-term human survival and long-term human residence, respectively. To study the effects of hypobaric-hypoxic environments on pulmonary vascular beds, the physiologic and morphometric differences occurring in the pulmonary arteries of rats at the equivalent of these two altitude levels were compared. One hundred and ninety male rats were housed in a double-roomed mechanical chamber and subjected for 12 weeks to hypobaric-hypoxic environments equivalent to an altitude level of 5500 m or 4000 m. After 6-8 weeks, mean pulmonary arterial pressure (PAPm) was significantly higher in rats at the 5500 m level than in those at 4000 m. The external diameter of muscular arteries (M) and of partially muscular arteries (PM) in the lungs of rats at 8 and 12 weeks, and those of nonmuscular arteries (NM) around the alveolar sacs at 2 and 8 weeks were each significantly less in rats exposed to the 5500 m level than in those at 4000 m. At 4 weeks, the ratio of medial thickness to external diameter for M and PM around the alveolar ducts and alveolar sacs were greater in rats exposed to the 5500 m level than in those at 4000 m. Erythrocyte count, hemoglobin and hematocrit tests showed polycythemic patterns during the initial hypobaric period in both 5500 m-, and 4000 m-level rats. However, from 4 to 12 weeks, the hematologic values of the 4000 m-level rats declined progressively toward the upper end of the normal range. This study suggests (i) that elevated PAPm in rats exposed to hypobaric-hypoxic environments results from structural remodeling of all M, PM and NM within the lobule, and (ii) that an environment equivalent to the 5500 m level causes more severe pulmonary vascular changes than one equivalent to the 4000 m level. The hematologic results suggest that rats exposed to the equivalent of the upper limit for long-term human residence can acquire acclimatization, but not those exposed to the equivalent of the upper limit for short-term human survival.