TY - JOUR AU - Kaya Tijen AU - Gursoy Sinan AU - Karadas Baris AU - Sarac Bulent AU - Kafali Haluk AU - Soydan Ahmet Serdar PY - 2016 TI - High-concentration tramadol-induced vasodilation in rabbit aorta is mediated by both endothelium-dependent and -independent mechanisms. JF - Acta Pharmacologica Sinica; Vol 24, No 5 (May 2003): Acta Pharmacologica Sinica Y2 - 2016 KW - N2 - 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), NG-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 x 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 indomethacin (10(-5) mol/L), glibenclamide (10(-5) mol/L), TEA (10(-3) mol/L), and naloxone (10(-4) mol/L) had no effect on the tramadol-induced relaxation. In endothelium-intact rings, L-NAME (10(-4) mol/L) pretreatment caused marked inhibition of the relaxation induced by tramadol, but not endothelium-denuded rings. CONCLUSION: In the rabbit aorta, vascular relaxation induced by tramadol is due to both nitric oxide production from endothelium and a direct effect on smooth muscle. UR - http://www.chinaphar.com/article/view/9101