Mechanism of pathophysiological effects of diesel exhaust particles on endothelial cells.

The suspension of diesel exhaust particles (DEP) inhibited endothelium-dependent relaxation (EDR). The mechanism of the impairment of EDR by DEP was investigated with cultured porcine endothelial cells (PEC) and NO synthase (NOS) cell free system. Incubation of PEC with DEP (50-150 μg/ml) for 10-30 min did not induce cell damage. Bradykinin-induced endothelium-dependent relaxing factor (EDRF) release from PEC was bioassayed by cyclic GMP formation in RFL-6 cells. A 10-min preincubation of PEC with DEP (0.1-100 μg/ml) inhibited EDRF release. NOS activity from rat cerebellum cytosol was measured either by the conversion of 3H-l-arginine to (3)H-l-citrulline or the NO(2)(-) formation. A 10-min preincubation of NOS with DEP (0.1-100 μg/ml) did not affect the formation of (3)H-l-citrulline. In contrast, it inhibited NO(2)(-) formation. These results suggest that DEP neither induced cell damage nor inhibited EDRF release from PEC, but DEP scavenged NO to block its physiological action.