Protein synthesis in the rat pulmonary trunk during the early development of hypoxia-induced pulmonary hypertension.

The purpose of this study was to determine the temporal alterations in protein synthesis and accumulation in the rat pulmonary trunk during the early development of hypoxia-induced pulmonary hypertension and to correlate these results with the pattern of development of polycythemia, right ventricular hypertrophy (RVH) and increased right ventricular pressure (RVP). In vitro synthesis of collagen and noncollagen protein was determined in the pulmonary trunks (PT) of rats exposed to chronic hypobaric hypoxia (0.5 atm/380 Torr) for 3, 7, 10, 14 or 21 days and in respective control groups of pair-fed normoxic rats. In vitro collagen synthesis was increased 1,150% (p less than 0.01) in PT from rats exposed to hypoxia for 3 days compared to PT from normoxic rats. When duration of hypoxic exposure increased, the percentage increase in collagen synthesis in PT from hypoxic vs. normoxic rats declined but remained significantly elevated (340%, p less than 0.005) after 21 days. Comparison of in vitro synthesis of noncollagen protein demonstrated a similar pattern of alteration with increasing hypoxic exposure. Synthesis of noncollagen protein was increased 750% in PT from hypoxic rats compared to normoxic controls at 7 days (p less than 0.0005) and decreased in parallel with collagen synthesis until 21 days when the difference in mean noncollagen protein synthesis was no longer statistically significant. In contrast, the accumulation of protein in vitro during hypoxic exposure, as determined from measurement of absolute protein and hydroxyproline content, demonstrated a pattern of continued increase with hypoxic exposure. Absolute protein content (microgram protein/vessel) was increased 330% in PT from hypoxic rats after 3 days compared to controls (p less than 0.005). By 21 days, mean absolute protein content of hypoxic PT was increased 500% compared to controls (p less than 0.0005). Absolute hydroxyproline content became significantly elevated in PT from hypoxic rats compared to controls after 7 days (123%, p less than 0.005 and the difference increased to 135% at 21 days (p less than 0.025). From comparison of these results with the pattern of changes in established indicators of pulmonary hypertension, herein reproduced, it is deduced that increased protein synthesis is a very early response of the pulmonary trunk to the stimulus of increased arterial blood pressure. Protein synthesis then declines while accumulation increases in a manner which suggests that the newly synthesized protein alters the response of the vessel to the continuing stimulus. It is proposed that increased accumulation of protein, particularly collagen, decreases the distension of the vessel wall caused by increased transmural pressure.