Expression of platelet-derived growth factor in pulmonary arteries in rats with high-altitude environment-induced pulmonary hypertension and its regulation by bosentan

AIM: To establish the rat model of high-altitude environment-induced pulmonary hypertension,observe proliferative changes in pulmonary arterial smooth muscle of hypoxic pulmonary vascular remodeling and to explore the effect of bosentan on high-altitude environment-induced pulmonary hypertension in rats and on the expression of platelet-derived growth factor(PDGF) in pulmonary artery in rats with high-altitude environment-induced pulmonary hypertension.METHODS: Rats were exposed to low-pressure and low-oxygen conditions in a self-modulating hypobaric and hypoxic cabin(air pressure 50 kPa,oxygen concentration 10%) to establish the high-altitude environment-induced pulmonary hypertension animal model.Forty male Sprague Dawley rats were randomly divided into four groups: control group,hypoxia group,placebo group and bosentan group.Rats in the control group remained in an orthobaric environment while rats in other groups were kept in hypobaric chamber for 8 h,1 day for 3 weeks,6 weeks and 6 weeks.After 3 weeks' exposure to hypobaric hypoxic environment,sodium chloride(2 ml) or bosentan(100 mg/kg) was administrated to placebo group and bosentan group for another 3 weeks.To observe the morphological changes of pulmonary vessels in rats,immunohistochemical technique was used to assess the abundance and localization of platelet-derived growth factor in pulmonary arteries.RESULTS: Thickening and stenosis of pulmonary arteries were observed in placebo group and bosentan reversed the changes.PDGF was expressed in pulmonary arteries in all four groups and the expression of PDGF increased with the increasing time of hypoxia.CONCLUSION: Bosentan successfully reversed hypoxic pulmonary vascular remodeling,suggesting that bosentan may be used to treat high-altitude environment-induced pulmonary hypertension.Bosentan may have a suppressible effect on the expression of PDGF in rats with high-altitude environment-induced pulmonary hypertension.