Lidocaine has been demonstrated to modify both contraction and relaxation of the vascular smooth muscle. Although lidocaine has been shown to inhibit endothelium-independent relaxations, the effects of lidocaine on arterial relaxation induced by peroxynitrite, a reaction product of superoxide and nitric oxide, have not been studied. The current study was designed to evaluate the effects of lidocaine on endothelium-dependent and -independent relaxations in isolated rabbit thoracic aorta. Rings of the rabbit thoracic aorta with or without endothelium were mounted for isometric force recording. Concentration-response curves to calcium ionophore A23187 ( 10(-9)to 3 x 10(-6)m), acetylcholine ( 10(-9)to 10(-3)m), sodium nitroprusside (SNP, 10(-9)to 10(-3)m), and peroxynitrite ( 10(-9)to 10(-3)m) were obtained in a cumulative manner. Lidocaine ( 10(-6)to 10(-4)m) was applied 15 min before addition of phenylephrine. Under resting force, lidocaine produced contractions at high concentrations ( 10(-5)to 10(-2)m) in endothelium-intact and -denuded arteries but removal of the endothelium did not significantly affect contractile activity. In phenylephrine-precontracted arteries, lidocaine caused concentration-dependent relaxations in both endothelium-intact and -denuded arteries. Inhibition of nitric oxide synthase or removal of endothelium did not affect the relaxations to lidocaine. Lidocaine suppressed the endothelium-independent relaxations of peroxynitrite, also poly (ADP-ribose) synthetase (PARS) enzyme activator, and SNP at high concentrations. Concentration-dependent vascular relaxations to A23187 and acetylcholine were significantly inhibited by lidocaine. These results suggest that lidocaine can depress vascular relaxations by a complex mechanism including inhibition of PARS enzyme activity.