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


CONCLUSIONS
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.
Cho
Hyoung-Chan
HC
Department of Anesthesia and Pain Medicine, Gyeongsang National University Hospital, 90 Chilam-dong, Jinju, Gyeongnam, Republic of Korea.
Sohn
Ju-Tae
JT
Park
Kyeong-Eon
KE
Shin
Il-Woo
IW
Chang
Ki Churl
KC
Lee
Jae-Wan
JW
Lee
Heon-Keun
HK
Chung
Young-Kyun
YK
D000701:Analgesics, Opioid / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D001011:Aorta / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000494:pharmacology; D019806:Cromakalim / Q000494:pharmacology; D003627:Data Interpretation, Statistical; D004110:Diltiazem / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005905:Glyburide / Q000494:pharmacology; D007004:Hypoglycemic Agents / Q000494:pharmacology; D066298:In Vitro Techniques; D054086:KATP Channels; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D026902:Potassium Channel Blockers / Q000494:pharmacology; D024661:Potassium Channels, Inwardly Rectifying / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013237:Stereoisomerism; D014147:Tramadol / Q000737:chemistry / Q000494:pharmacology*
D000701:Analgesics, Opioid; D002121:Calcium Channel Blockers; D007004:Hypoglycemic Agents; D054086:KATP Channels; D026902:Potassium Channel Blockers; D024661:Potassium Channels, Inwardly Rectifying; C092520:uK-ATP-1 potassium channel; D019806:Cromakalim; D014147:Tramadol; D004110:Diltiazem; D005905:Glyburide