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

[Effet inhibiteur du tramadol sur la vasorelaxation médiée par les canaux potassiques sensibles à l’ATP de l’aorte du rat]

Hyoung-Chan Cho, MD, Ju-Tae Sohn, MD^*,, Kyeong-Eon Park, MD^*, Il-Woo Shin, MD^*,, Ki Churl Chang, PhD^,, Jae-Wan Lee, MD^*, Heon-Keun Lee, MD^* and Young-Kyun Chung, MD^*

^* From the Department of Anesthesia and Pain Medicine, the
Department of Pharmacology, and the
Institute of Health Sciences, Gyeongsang National University School of Medicine; and the
Department of Anesthesia, Seoul E. N. T. Hospital, Gyeongnam, Republic of Korea.

Address correspondence to: Dr. Ju-Tae Sohn, Department of Anesthesia and Pain Medicine, Gyeongsang National University Hospital, 90 Chilam-dong, Jinju, Gyeongnam, 660-702, Republic of Korea. Phone: +82-55-750-8586; Fax: + 82-55-750-8142; E-mail: jtsohn{at}nongae.gsnu.ac.kr

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 x 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 x 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 x 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.