Increased Intraluminal Pressure Induces DNA Synthesis and c-fos Expression in Perfused Rat Aorta

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Abstract
The molecular mechanisms responsible for the vascular hypertrophy observed in the arteries of hypertensive subjects are poorly understood. In this study, we tested the hypothesis that an increase in intraluminal pressure could by itself induce some of the vascular changes associated with hypertension, such as increased DNA synthesis and c-fos expression. We perfused rat thoracic aortae at different pressures for up to 4 h. The perfusion system consisted of a peristaltic pump and a closed circuit of plastic tubing connected to a culture media bottle where rat thoracic aortae were placed. After a 30 min equilibration period at 20 mm Hg, the perfusion pressure was adjusted to “normotensive levels” (132 ± 3 / 59 ± 4 mm Hg) or “hypertensive levels” (204 ± 5 / 74 ± 8 mm Hg). 3 H-Thymidine was added at this time. After 4 h, the arteries were removed from the apparatus. Tunica media and adventitia were separated and processed for scintillation counting. 3 H-Thymidine incorporation was 39% higher in the “hypertensive” than in the “normotensive” arteries. In separate experiments, after a 20 min equilibration period, the arteries were perfused for an additional 30 min at 50/10, 100/35, or 150/50 mm Hg. After being removed from the perfusion apparatus, the arteries were homogenized and total RNA was isolated. c-fos Expression was analyzed by Northern blot. c-fos Expression corresponded directly with the perfusion pressure. The highest levels of c-fos expression were detected in the arteries exposed to the highest pressures. These findings support the hypothesis that hemodynamic and/or mechanical factors can influence cell growth and function.