IMPAIRMENT OF ENDOTHELIUM-DEPENDENT RELAXATION BY DIESEL EXHAUST PARTICLES IN RAT THORACIC AORTA

Nitric oxide released from vascular: endothelium plays important regul atory roles in cardiovascular and pulmonary systems. Epidemiological s tudies suggest that diesel exhaust particles (DEP) seem to be one of t he causative factors responsible for the recent increase in pulmonary diseases, To clarify the pathogenic mechanism, the effects of DEP on v ascular endothelial functions were investigated in terms of endotheliu m-dependent relaxation. Ring preparations of rat thoracic aorta were p reincubated for 10 min with a DEP suspension (1, 10, 100 mu g/ml) at 3 7 degrees C in organ baths and relaxed with cumulative additions of ac etylcholine following precontraction with phenylephrine (10(-6) M). Th e relaxation was attenuated by DEP-exposure in a concentration-depende nt manner. An addition of superoxide dismutase (SOD) completely abolis hed the inhibitory effect of DEP at lower concentrations, but only par tially at the higher concentration. DEP (10 mu g/ml) neither affected the contractile response to phenylephrine in intact aortic rings nor t he endothelium-independent relaxation by sodium nitroprusside in denud ed rings, while DEP (100 mu g/ml) significantly attenuated both respon ses. These results suggest that 1) inhaled DEP causes pulmonary inflam mation by inhibiting the endothelial formation and/or the effect of ni tric oxide and 2) SOD reduces the adverse effects.