Caffeic acid phenethyl ester (CAPE) is a naturally occurring compound isolated from honeybee propolis whose cardiovascular properties remain uncertain. The purpose of this study was to investigate the possible mechanisms of CAPE-induced vasorelaxation in porcine coronary artery rings. It was found that both the quiescent and precontracted coronary artery ring segments were relaxed by CAPE (10(-7)-10(-)(4) M). N(omega)-nitro-l-arginine (L-NNA), methylene blue and removal of endothelium significantly attenuated CAPE-induced relaxation of both quiescent and precontracted artery rings. This relaxing effect of CAPE on coronary arteries was also significantly reduced by propranolol, and SQ22536, but not by indomethacin. In addition, the dose-response curves of KCl (2.5-100 mM) and CaCl(2) (10(-5)-10(-2) M) were displaced downwards in the presence of CAPE. These results suggest that the relaxant effect of CAPE on porcine coronary artery rings might involve the action of nitric oxide (NO) and adrenergic beta-receptor, together with their second messenger, cyclic guanosine monophosphate (cGMP) and cyclic adenosine monophosphate (cAMP), respectively, but not involve the synthesis of prostaglandin.