STATIC TENSION IS ASSOCIATED WITH INCREASED SMOOTH-MUSCLE CELL-DNA SYNTHESIS IN RAT PULMONARY-ARTERIES

During the development of pulmonary hypertension, vascular cell prolif eration 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) wa s applied to hilar pulmonary arterial rings cultured in a serum-free m edium. Incorporation of the thymidine analogue, bromodeoxyuridine (Brd U), into medial and adventitial cells was analyzed by immunohistochemi stry. Medial cell BrdU incorporation (%positive cells) was increased ( P < 0.0001) at all levels of force compared with 0-g controls (unmount ed 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 arteri es attenuated (P < 0.05) tension-induced medial cell BrdU labeling (2. 5 +/- 0.96 and 3.3 +/- 0.63, respectively) compared with control arter ies (6.0 +/- 0.54). Nifedipine reduced tension-induced medial cell Brd U incorporation (P < 0.05). There was no difference in DNA synthesis i n adventitial cells at the various levels of force, although hypoxia d ecreased adventitial cell BrdU incorporation overall (P < 0.05). We co nclude that static wall tension may be an important direct stimulus fo r medial cell DNA synthesis.