title: Levobupivacaine-induced contraction of isolated rat aorta is calcium dependent.
abstract: Levobupivacaine is a long-acting local anesthetic that intrinsically produces vasoconstriction in isolated vessels. The goals of this study were to investigate the calcium-dependent mechanism underlying levobupivacaine-induced contraction of isolated rat aorta in vitro and to elucidate the pathway responsible for the endothelium-dependent attenuation of levobupivacaine-induced contraction. Isolated rat aortic rings were suspended to record isometric tension. Cumulative levobupivacaine concentration-response curves were generated in either the presence or absence of the antagonists verapamil, nifedipine, SKF-96365, 2-aminoethoxydiphenylborate, Gd(3+), N(W)-nitro-l-arginine methyl ester (L-NAME), 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ), and methylene blue, either alone or in combination. Verapamil, nifedipine, SKF-96365, 2-aminoethoxydiphenylborate, low calcium concentrations, and calcium-free Krebs solution attenuated levobupivacaine-induced contraction. Gd(3+) had no effect on levobupivacaine-induced contraction. Levobupivacaine increased intracellular calcium levels in vascular smooth muscle cells. L-NAME, ODQ, and methylene blue increased levobupivacaine-induced contraction in endothelium-intact aorta. SKF-96365 attenuated calcium-induced contraction in a previously calcium-free isotonic depolarizing solution containing 100 mmol/L KCl. Levobupivacaine-induced contraction of rat aortic smooth muscle is mediated primarily by calcium influx from the extracellular space mainly via voltage-operated calcium channels and, in part, by inositol 1,4,5-trisphosphate receptor-mediated release of calcium from the sarcoplasmic reticulum. The nitric oxide - cyclic guanosine monophosphate pathway is involved in the endothelium-dependent attenuation of levobupivacaine-induced contraction.
authors.affiliation: Department of Anesthesiology and Pain Medicine, Gyeongsang National University Hospital, Jinju, Korea.
authors.forename: Ji Seok
authors.initials: JS
authors.lastname: Baik
authors.forename: Ju-Tae
authors.initials: JT
authors.lastname: Sohn
authors.forename: Seong-Ho
authors.initials: SH
authors.lastname: Ok
authors.forename: Jae-Gak
authors.initials: JG
authors.lastname: Kim
authors.forename: Hui-Jin
authors.initials: HJ
authors.lastname: Sung
authors.forename: Sang-Seung
authors.initials: SS
authors.lastname: Park
authors.forename: Jae-Yong
authors.initials: JY
authors.lastname: Park
authors.forename: Eun Mi
authors.initials: EM
authors.lastname: Hwang
authors.forename: Young-Kyun
authors.initials: YK
authors.lastname: Chung
mesh_terms: D000779:Anesthetics, Local / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000187:drug effects* / Q000378:metabolism*; D002045:Bupivacaine / Q000031:analogs & derivatives / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D000077554:Levobupivacaine; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012519:Sarcoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism; D014661:Vasoconstriction / Q000187:drug effects*
chemical_list: D000779:Anesthetics, Local; D015220:Calcium Channels; D009569:Nitric Oxide; D000077554:Levobupivacaine; D006152:Cyclic GMP; D002118:Calcium; D002045:Bupivacaine