Diesel exhaust particles induce endothelial dysfunction in apoE−/− mice

Background: Particulate air pollution can aggravate cardiovascular disease by mechanisms suggested to involve translocation of particles to the bloodstream and impairment of endothelial function, possibly dependent on present atherosclerosis. Aim: We investigated the effects of exposure to diesel exhaust particles (DEP) in vivo and ex vivo on vasomotor functions in aorta from apoE−/− mice with slight atherosclerosis and from normal apoE+/+ mice. Methods: DEP 0, 0.5 or 5 mg/kg bodyweight in saline was administered i.p. The mice were sacrificed 1 h later and aorta ring segments were mounted on wire myographs. Segments from unexposed mice were also incubated ex vivo with 0, 10 and 100 μg DEP/ml before measurement of vasomotor functions. Results: Exposure to 0.5 mg/kg DEP in vivo caused a decrease in the endothelium-dependent acetylcholine elicited vasorelaxation in apoE−/− mice, whereas the response was enhanced in apoE+/+ mice. No significant change was observed after administration of 5 mg/kg DEP. In vivo DEP exposure did not affect constriction induced by K+ or phenylephrine. In vitro exposure to 100 μg DEP/ml enhanced acetylcholine-induced relaxation and attenuated phenylephrine-induced constriction. Vasodilation induced by sodium nitroprusside was not affected by any DEP exposure. Conclusion: Exposure to DEP has acute effect on vascular functions. Endothelial dysfunction possibly due to decreased NO production as suggested by decreased acetylcholine-induced vasorelaxation and unchanged sodium nitroprusside response can be induced by DEP in vivo only in vessels of mice with some atherosclerosis.