Chronic hypoxic exposure causes pulmonary hypertension and right ventricular hypertrophy associated with pulmonary vascular remodeling in rats. Since platelet-activating factor (PAF) production has been shown to increase during hypoxia, and since PAF contributes to pulmonary hypertension, we hypothesized that increased PAF during hypoxia might play a role in the development of pulmonary hypertension induced by hypoxic exposure, and examined the effect of PAF-antagonists on hypoxia-induced pulmonary hypertension. Pulmonary hypertension and right ventricular hypertrophy developed at 3 weeks of hypoxic exposure. Treatment with WEB 2170 or BN 50739, specific PAF-antagonists significantly reduced hypoxia-induced pulmonary hypertension. Hypoxia-induced pulmonary hypertension was associated with an increase in the vessel wall thickness of the muscular arteries. In WEB 2170-treated rats, this change was significantly less severe than that observed in untreated chronically hypoxic rats. These results indicate that the PAF-antagonists inhibit the development of pulmonary hypertension induced by chronic hypoxic exposure and suggest a role for PAF in the remodeling process of pulmonary vessels induced by chronic hypoxia in rats.
