Eugenol is a natural pungent substance and the main component of clove oil, with vasorelaxant action. To elucidate some of the possible mechanisms involved in this action isometric tension was measured in aortic rings from male Wistar rats precontracted with phenylephrine (PHE, 10(-7) M) or KCl (75 mM). Responses to increasing concentrations of eugenol (10(-6)-10(-2) M) were obtained in the presence and absence of endothelium. In the presence of eugenol, dose-response curves to PHE (10(-9) to 10(-4) M) and KCl (5-125 mM) were displaced downwards. Concentration-dependent relaxation was observed in rings precontracted with PHE (10(-7) M) and KCl (75 mM). The tension increment produced by increasing external calcium concentration (0.25-3 mM) was also reduced by eugenol (300 microM) treatment. The inhibitory effects of eugenol (300 microM) were compared to those induced by nifedipine (0.01 microM), a selective Ca(2+) channel blocker, producing similar relaxant effects. Two other protocols were performed. After precontraction with PHE (10(-7) M), increasing concentrations of eugenol (10(-6)-10(-2) M) were used before and after N(w)-nitro-L-arginine (L-NAME, 10(-4) M) and methylene blue (10(-5) M) treatment. Eugenol-induced relaxation was reduced by endothelial damage (rubbing), L-NAME and methylene blue treatments. Results suggested that eugenol produces smooth muscle relaxation resulting from the blockade of both voltage-sensitive and receptor-operated channels that are modulated by endothelial-generated nitric oxide.