Relationship of the Pulmonary Vascular Endothellum to Altered Pulmonary Vascular Resistance*

CHEST I 93 I 3 I MARCH, 1988 I Supplement 101$ activity. Contractile responses of MPA and SPA to high K , norepinephrine, and serotonin were studied. A regular sequence of changes in response was observed during exposure to chronic hypoxia (Fig 2). Both maximal active wall stress and tension in response to 120 mMK were decreased in MPA of 2-day hypoxic rats (Fig 2A and B). The weight of the segments increased only after 5 days. After 15 days, both wall stress and total tension increased again, but stress remained less than in the control, while at 20 days tension was greater than in the normoxic. Exainination of the weights of the segments (Fig 2C) shows clearly that weight changes cannot account for the diminution in stress and tension from days 1-5 nor the increase in both from days 10-20. The final sustained increase in total tension in the hypoxic, however, reflects the increased segment weight. It is probably attributable to hypertrophy or hyperplasia. The wall stress data suggest that although the segments produce greater total tension, tension production per SMC is diminished. In addition to physiologic observations, immunocytochemical and biochemical (1and 2-dimensional SDS gels) studies of the cytoskeletal proteins desmin and vimentin showed that the content and distribution of desmin alters during the first 20 days of chronic alveolar hypoxia. The common practice of examining changes in structure and function of pulmonary arteries in rats at day 14 of chronic hypoxia may be misleading. All of our observations indicate that day 14 is the approximate midpoint of a transition period, dominated by processes which lead to the alterations in vessel wall structure and cell function characteristic of the pulmonary hypertensive. Day 14 is therefore an appropriate time to study the transition, not the stabilized characteristics of the hypertensive. We followed the temporal sequence of changes in function to analyze mechanisms controlling the development of pulmonary hypertension. We were especially interested in the coincidence of the time course of rise and fall in spontaneous rhythmic activity with decrease and increase in wall stress and tension. We suggest that these phenomena reflect different expressions of phenotypic modulation of pulmonary arterial SMC during the development of pulmonary hypertension and thus represent an ideal starting point for analysis of the mechanisms controlling this process.