title: A supraclinical dose of tramadol stereoselectively attenuates endothelium-dependent relaxation in isolated rat aorta.
abstract: Tramadol, a combination of R(-) and S(+) enantiomers, inhibits both the acetylcholine-mediated response of muscarinic receptors and the muscarine-induced accumulation of cyclic guanosine monophosphate. Our goals in this in vitro study were to investigate the effects of tramadol on endothelium-dependent relaxation induced by acetylcholine, to determine whether this effect of tramadol is stereoselective, and to elucidate the associated cellular mechanism in rat aorta. In endothelium-intact rings precontracted with phenylephrine with or without naloxone, dose-response curves for acetylcholine, histamine, and calcium ionophore A23187 were generated in the presence and absence of tramadol (racemic, R(-) and S(+)). Sodium nitroprusside dose-response curves were generated in the presence and absence of racemic tramadol. Racemic tramadol (5 x 10(-5) 10(-4) M) attenuated acetylcholine-induced relaxation in the rings with or without naloxone. R(-) tramadol, 5 x 10(-5) M, attenuated acetylcholine-induced relaxation, whereas S(+) tramadol, 5 x 10(-5) M, did not. Racemic tramadol (10(-4) M) had no effect on dose-response curves for calcium ionophore A23187 or sodium nitroprusside. Taken together, these results indicate that tramadol, at a supraclinical dose (5 x 10(-5) M), stereoselectively attenuates endothelium-dependent relaxation via an inhibitory effect at levels proximal to nitric oxide synthase activation on a pathway involving nonspecific endothelial receptor activation.
authors.affiliation: Department of Anesthesia and Pain Medicine, Gyeongsang National University College of Medicine, Jinju, Gyeongnam, Republic of Korea.
authors.forename: Il-Woo
authors.initials: IW
authors.lastname: Shin
authors.forename: Ju-Tae
authors.initials: JT
authors.lastname: Sohn
authors.forename: Kyeong-Eon
authors.initials: KE
authors.lastname: Park
authors.forename: Ki Churl
authors.initials: KC
authors.lastname: Chang
authors.forename: Ju-Young
authors.initials: JY
authors.lastname: Choi
authors.forename: Heon-Keun
authors.initials: HK
authors.lastname: Lee
authors.forename: Young-Kyun
authors.initials: YK
authors.lastname: Chung
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000502:physiology*; D066298:In Vitro Techniques; D008297:Male; D009569:Nitric Oxide / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013237:Stereoisomerism; D014147:Tramadol / Q000494:pharmacology*; D014664:Vasodilation / Q000187:drug effects*
chemical_list: D000701:Analgesics, Opioid; D009569:Nitric Oxide; D014147:Tramadol; D000109:Acetylcholine