Inhibitory effect of tramadol on vasorelaxation mediated by ATP-sensitive K+ channels in rat aorta

Abstract

Purpose: Tramadol produces a conduction block similar to lidocaine by exerting a local anesthetic-like effect. The aims of this in vitro study were to determine the effects of tramadol on the vasorelaxant response induced by the adenosine triphosphate-sensitive K + (K ATP ) channel opener, levcromakalim, in an endothelium-denuded rat aorta, and to determine whether this effect of tramadol is stereoselective. Methods:The effects of tramadol (racemic, R(-) and S(+): 10 -6 , 10 -5 , 5 × 10 -5 M), and glibenclamide on the levcromakalim dose-response curve were assessed in aortic rings that had been pre-contracted with phenylephrine. In the rings pretreated independently with naloxone, and glibenclamide, the levcromakalim dose-response curves were generated in the presence or absence of tramadol. The effect of tramadol on the dose-response curve of diltiazem was assessed.Results: Racemic, R(-) and S(+) tramadol (10 -5 , 5 × 10 -5 M) attenuated (P < 0.0001) levcromakalim-induced relaxation in the ring with or without naloxone in a dose-dependent manner. The magnitude of the R(-)-tramadol-induced attenuation of vasorelaxant response induced by levcromakalim was greater (P < 0.05) than that induced by S(+)-tramadol. Glibenclamide almost abolished the levcromakalim-induced relaxation. Tramadol, 5 × 10 -5 M, did not significantly alter the diltiazem-induced relaxation. Conclusion: These results suggest that a supraclinical dose (10 -5 M) of tramadol [racemic, R(-) and S(+)] attenuates the vasorelaxation mediated by the K ATP channels in the rat aorta. The R(-) tramadol-induced attenuation of vasorelaxation induced by levcromaklim was more potent than that induced by S(+) tramadol. This attenuation is independent of opioid receptor activation. Méthode : Les effets du tramadol (racémique, R(-) et S(+) : 10 -6 , 10 -5 , 5 × 10 -5 M), et du glibenclamide sur la courbe dose-réponse du levcromakalim ont été évalués sur des anneaux aortiques pré-contractés avec de la phényléphrine. Sur les anneaux indépendam-ment prétraités au naloxone et au glibenclamide, les courbes de dose-réponse du levcromakalim ont été générées en présence ou en l'absence de tramadol. L'effet du tramadol sur la courbe doseréponse du diltiazem a été évalué. Résultat : Le tramadol racémique R(-) et S(+) a atténué (P <

Effects of chronic tramadol exposure on the zebrafish brain: A proteomic study

“…On the other hand, it may also be a regulator of ion channels. As examples, it inhibits 5-HT-induced Ca 2+ -activated-Cl − current [5], delayed rectifier K + current [6], and a supraclinical dose attenuates the vasorelaxation mediated by the K ATP channels in the rat aorta [7]. Although the analgesic effects of tramadol are thought to result from the sum of these, the detailed mechanisms have not yet been completely clarified.…”

Comparative Effects of Tramadol on Vascular Reactivity in Normotensive and Spontaneously Hypertensive Rats

“…Similarly, Kaya et al 25 showed that ATPsensitive and Ca 2+ -activated K + channels are not involved in the vasodilator action of tramadol in rabbit isolated aorta. Conversely, Cho et al 26 demonstrated that tramadol attenuates vasorelaxant responses to ATP-sensitive K + channel activation in normotensive rat aorta.…”