Acrolein is a highly reactive aldehyde pollutant and an endogenous product of lipid peroxidation. Increased generation of, or exposures to, acrolein incites pulmonary and vascular injury. The effects of acrolein on the vasomotor responses of rat aortic rings were studied to understand its mechanism of action. Incubation with acrolein (10-100 microM) alone did not affect the resting tone of aortic vessels; however, a dose-dependent relaxation of phenylephrine-precontracted aortic rings was observed. Acrolein-induced relaxation was slow and time dependent and the extent of relaxation after 100 min of application was 44.7 +/- 4.1% (10 microM), 56.0 +/- 5.6% (20 microM), 61.0 +/- 7.9% (40 microM), and 96.1 +/- 2.1 (80 microM), respectively, versus 14.2 +/- 3.3% relaxation in the absence of acrolein. Acrolein-induced vasorelaxation was prevented by endothelial denudation and was abolished on pretreatment with the nitric oxide synthase inhibitor Nomega-nitro-L-arginine methyl ester, the guanylyl cyclase inhibitor 1H-[1,2,4]oxidazolo[4,3-a]quinoxaline-1-one, or the cyclooxygenase inhibitor indomethacin. Inhibition of K+ channels (by tetrabutylammonium) or Na+-K+-ATPase (by ouabain) did not significantly prevent acrolein-mediated vasorelaxation. Exposure to acrolein in the presence or absence of other compounds elicited slow wave vasomotor effect in 77% of aortic vessels versus 1.4% in control. Vasomotor responses were also studied on aortic rings prepared from rats fed 2 mg. kg-1. day-1 acrolein for 3 alternate days by oral gavage. These vessels developed a significantly lower contractile response to phenylephrine compared with controls. Together, these results indicate that acute acrolein exposure evokes delayed vasorelaxation due to a nitric oxide- and prostacyclin-dependent mechanism, whereas in vivo acrolein exposure compromises vessel contractility.