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


CONCLUSIONS
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.
Department of Pharmacology, Cumhuriyet University, Faculty of Medicine, Sivas 58140, Turkey. tkaya@cumhuriyet.edu.tr
Tijen
T
Kaya
Sinan
S
Gursoy
Baris
B
Karadas
Bulent
B
Sarac
Haluk
H
Fafali
Ahmet Serdar
AS
Soydan
D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D004730:Endothelium, Vascular / Q000502:physiology; D066298:In Vitro Techniques; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D011817:Rabbits; D014147:Tramadol / Q000008:administration & dosage / Q000494:pharmacology*; D014664:Vasodilation / Q000187:drug effects*
D000701:Analgesics, Opioid; D014147:Tramadol; D019331:NG-Nitroarginine Methyl Ester