AIM: The mechanism of tramadol-induced vasodilation was investigated using isolated rabbit thoracic aortic rings. METHODS: Aortic rings from 8 rabbits were placed in organ bath and precontracted with phenylephrine(10~(-5) mol/L) before addition of tramadol. Relaxation responses by tramadol were evaluated in the presence and absence of endothelium, indomethacin (an inhibitor of cyclooxygenase), N~G-nitro-L-arginine methyl ester (L-NAME, a specific inhibitor of nitric oxide synthase), glibenclamide (an inhibitor of ATP-sensitive potassium channels), tetraethylammonium chloride (TEA, an inhibitor of calcium-sensitive potassium channels), and naloxone (an antagonist of opioid receptors). RESULTS: Tramadol(10~(-4) mol/L and 3×10~(-4) mol/L) caused significant vasodilation in endothelium-intact and endothelium-denuded aortic rings (P<0.05). The relaxation response to tramadol was significantly greater in endothelium-intact rings than in endothelium-denuded rings. Pretreatment of aortic rings with indomethaci AIM: The mechanism of tramadol-induced vasodilation was investigated using isolated rabbit thoracic aortic rings. METHODS: Aortic rings from 8 rabbits were placed in organ bath and precontracted with phenylephrine (10 ~ (-5) mol / L) before addition of tramadol. Relaxation responses by tramadol were evaluated in the presence and absence of endothelium, indomethacin (an inhibitor of cyclooxygenase), N-G-nitro-L-arginine methyl ester (L-NAME, a specific inhibitor of nitric oxide synthase), glibenclamide inhibitor of ATP-sensitive potassium channels), tetraethylammonium chloride (TEA, an inhibitor of calcium-sensitive potassium channels), and naloxone (an antagonist of opioid receptors). RESULTS: Tramadol (10 -4 mol / L and 3 × 10 -4 mol / L) caused significant vasodilation in endothelium-intact and endothelium-denuded aortic rings (P <0.05). The relaxation response to tramadol was significantly greater in endothelium-intact rings than in endothelium-denuded rings. Pretreatment of aortic ring s with indomethaci