Static tension is associated with increased smooth muscle cell DNA synthesis in rat pulmonary arteries

During the development of pulmonary hypertension, vascular cell proliferation closely parallels the rise in pulmonary intravascular pressure. The possible direct physical effect that elevated pressures may have on inducing vascular cell proliferation in pulmonary hypertension is unclear. To address this question, static force (0, 1, 5, and 10 g) was applied to hilar pulmonary arterial rings cultured in a serum-free medium. Incorporation of the thymidine analogue, bromodeoxyuridine (BrdU), into medial and adventitial cells was analyzed by immunohistochemistry. Medial cell BrdU incorporation (%positive cells) was increased (P < 0.0001) at all levels of force compared with 0-g controls (unmounted and mounted, but without applied force) (unmounted: 0.65 +/- 0.08; mounted: 0 g, 1.8 +/- 0.39; 1 g, 3.7 +/- 0.35; 5 g, 5.2 +/- 0.43; 10 g, 2.8 +/- 0.17). Hypoxia exposure and endothelial denudation of arteries attenuated (P < 0.05) tension-induced medial cell BrdU labeling (2.5 +/- 0.96 and 3.3 +/- 0.63, respectively) compared with control arteries (6.0 +/- 0.54). Nifedipine reduced tension-induced medial cell BrdU incorporation (P < 0.05). There was no difference in DNA synthesis in adventitial cells at the various levels of force, although hypoxia decreased adventitial cell BrdU incorporation overall (P < 0.05). We conclude that static wall tension may be an important direct stimulus for medial cell DNA synthesis.