High-concentration tramadol-induced vasodilation in rabbit aorta is mediated by both endothelium-dependent and -independent mechanisms


Kaya T., Gursoy S., Karadas B., Sarac B. , Kafali H., Soydan A.

ACTA PHARMACOLOGICA SINICA, cilt.24, ss.385-389, 2003 (SCI İndekslerine Giren Dergi) identifier identifier identifier

  • Cilt numarası: 24 Konu: 5
  • Basım Tarihi: 2003
  • Dergi Adı: ACTA PHARMACOLOGICA SINICA
  • Sayfa Sayıları: ss.385-389

Özet

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 3x10(-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.