title: Ropivacaine-induced contraction is attenuated by both endothelial nitric oxide and voltage-dependent potassium channels in isolated rat aortae.
abstract: This study investigated endothelium-derived vasodilators and potassium channels involved in the modulation of ropivacaine-induced contraction. In endothelium-intact rat aortae, ropivacaine concentration-response curves were generated in the presence or absence of the following inhibitors: the nonspecific nitric oxide synthase (NOS) inhibitor N (ω) -nitro-L-arginine methyl ester (L-NAME), the neuronal NOS inhibitor N (ω) -propyl-L-arginine hydrochloride, the inducible NOS inhibitor 1400W dihydrochloride, the nitric oxide-sensitive guanylyl cyclase (GC) inhibitor ODQ, the NOS and GC inhibitor methylene blue, the phosphoinositide-3 kinase inhibitor wortmannin, the cytochrome p450 epoxygenase inhibitor fluconazole, the voltage-dependent potassium channel inhibitor 4-aminopyridine (4-AP), the calcium-activated potassium channel inhibitor tetraethylammonium (TEA), the inward-rectifying potassium channel inhibitor barium chloride, and the ATP-sensitive potassium channel inhibitor glibenclamide. The effect of ropivacaine on endothelial nitric oxide synthase (eNOS) phosphorylation in human umbilical vein endothelial cells was examined by western blotting. Ropivacaine-induced contraction was weaker in endothelium-intact aortae than in endothelium-denuded aortae. L-NAME, ODQ, and methylene blue enhanced ropivacaine-induced contraction, whereas wortmannin, N (ω) -propyl-L-arginine hydrochloride, 1400W dihydrochloride, and fluconazole had no effect. 4-AP and TEA enhanced ropivacaine-induced contraction; however, barium chloride and glibenclamide had no effect. eNOS phosphorylation was induced by ropivacaine. These results suggest that ropivacaine-induced contraction is attenuated primarily by both endothelial nitric oxide and voltage-dependent potassium channels.
authors.affiliation: Department of Anesthesiology and Pain Medicine, Gyeongsang National University School of Medicine, Jinju 660-772, Republic of Korea.
authors.forename: Seong-Ho
authors.initials: SH
authors.lastname: Ok
authors.affiliation: Department of Anesthesiology and Pain Medicine, Gyeongsang National University Hospital, Jinju 660-702, Republic of Korea.
authors.forename: Jeong Yeol
authors.initials: JY
authors.lastname: Han
authors.affiliation: Department of Anesthesiology and Pain Medicine, Gyeongsang National University Hospital, Jinju 660-702, Republic of Korea.
authors.forename: Hui-Jin
authors.initials: HJ
authors.lastname: Sung
authors.affiliation: Department of Anesthesiology and Pain Medicine, Gyeongsang National University Hospital, Jinju 660-702, Republic of Korea.
authors.forename: Seong Min
authors.initials: SM
authors.lastname: Yang
authors.affiliation: Department of Anesthesiology and Pain Medicine, Gyeongsang National University Hospital, Jinju 660-702, Republic of Korea.
authors.forename: Jungchul
authors.initials: J
authors.lastname: Park
authors.affiliation: Department of Physiology, Kwandong University College of Medicine, Gangneung 201-701, Republic of Korea.
authors.forename: Seong-Chun
authors.initials: SC
authors.lastname: Kwon
authors.affiliation: Department of Oral and Maxillofacial Surgery, Gyeongsang National University Hospital, Jinju 660-702, Republic of Korea.
authors.forename: Mun-Jeoung
authors.initials: MJ
authors.lastname: Choi
authors.affiliation: Department of Anesthesiology and Pain Medicine, Institute of Health Sciences, Gyeongsang National University School of Medicine, Gyeongsang National University Hospital, Jinju 660-772, Republic of Korea.
authors.forename: Ju-Tae
authors.initials: JT
authors.lastname: Sohn
mesh_terms: D000577:Amides / Q000494:pharmacology*; D000818:Animals; D001011:Aorta / Q000187:drug effects* / Q000378:metabolism; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D024642:Potassium Channels, Voltage-Gated / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077212:Ropivacaine; D014661:Vasoconstriction / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D000577:Amides; D004791:Enzyme Inhibitors; D024642:Potassium Channels, Voltage-Gated; D014665:Vasodilator Agents; D009569:Nitric Oxide; D000077212:Ropivacaine; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III