The inhibitory actions of eugenol on intracellular Ca2+ concentration ([Ca2+]i) and the contractions induced by excess extracellular K+ concentration ([K+]o) in rabbit thoracic aorta were investigated. Application of excess [K+]o solution (30-90 mM) produced contraction and increased the intensity of the Ca2+ fluorescence signal. Pretreatment with eugenol (> or =0.1 mM) reduced both the amplitude of contraction and the intensity of the Ca2+ fluorescence signal, but the contraction was more strongly affected than the [Ca2+]i. Application of eugenol (0.3 mM) to tissue precontracted by 90 mM [K+]o solution (immediately after the removal of the 90 mM [K+]o solution) slowed the decay of the [Ca2+]i signal, but it did not change the rate of relaxation. Carbonyl cyanide m-chlorophenylhydrozone (10 microM), a mitochondrial metabolic inhibitor, produced a reduction in tension despite a slight increase in [Ca2+]i when applied to muscle precontracted by 90 mM [K+]o solution. These results indicate that eugenol relaxes the rabbit thoracic aorta while suppressing the Ca2+-sensitivity and both the uptake and extrusion mechanisms for Ca2+. To judge from the similarities between its actions and those of metabolic inhibitors, eugenol may produce its actions at least partly through metabolic inhibition.