長期低酸素曝露による肺高血圧招来における血小板活性化因子の関与

Abstract

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.