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

• Published in: Acta pharmacologica Sinica Vol. 24; no. 5; pp. 385 - 389
• Main Authors: Kaya, Tijen, Gursoy, Sinan, Karadas, Baris, Sarac, Bulent, Fafali, Haluk, Soydan, Ahmet Serdar
• Format: Journal Article
• Language: English
• Published: United States 01-05-2003
• Subjects: Analgesics, Opioid - administration & dosage; Analgesics, Opioid - pharmacology; Animals; Aorta, Thoracic - drug effects; Endothelium, Vascular - physiology; In Vitro Techniques; NG-Nitroarginine Methyl Ester - pharmacology; Rabbits; Tramadol - administration & dosage; Tramadol - pharmacology; Vasodilation - drug effects
• ISSN: 1671-4083

The mechanism of tramadol-induced vasodilation was investigated using isolated rabbit thoracic aortic rings.
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).
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.
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.