title: Calcium sensitization involved in dexmedetomidine-induced contraction of isolated rat aorta.
abstract: Dexmedetomidine, a full agonist of the α2B-adrenoceptor that is mainly involved in vascular smooth muscle contraction, is primarily used for analgesia and sedation in intensive care units. High-dose dexmedetomidine produces hypertension in children and adults. The goal of this in vitro study was to investigate the role of the calcium (Ca(2+)) sensitization mechanism involving Rho-kinase, protein kinase C (PKC), and phosphoinositide 3-kinase (PI3-K) in mediating contraction of isolated rat aortic smooth muscle in response to dexmedetomidine. The effect of dexmedetomidine on the intracellular Ca(2+) level ([Ca(2+)]i) and tension was measured simultaneously. Dexmedetomidine concentration-response curves were generated in the presence or absence of the following antagonists: rauwolscine, Y 27632, LY 294002, GF 109203X, and verapamil. Dexmedetomidine-induced phosphorylation of PKC and membrane translocation of Rho-kinase were detected with Western blotting. Rauwolscine, Y 27632, GF 109203X, LY 294002, and verapamil attenuated dexmedetomidine-induced contraction. The slope of the [Ca(2+)]i-tension curve for dexmedetomidine was higher than that for KCl. Dexmedetomidine induced phosphorylation of PKC and membrane translocation of Rho-kinase. These results suggest that dexmedetomidine-induced contraction involves a Ca(2+) sensitization mechanism mediated by Rho-kinase, PKC, and PI3-K that is secondary to α2-adrenoceptor stimulation in rat aortic smooth muscle.
authors.affiliation: a Department of Anesthesiology and Pain Medicine, Gyeongsang National University Hospital, Jinju 660-702, Korea.
authors.forename: Jae-Gak
authors.initials: JG
authors.lastname: Kim
authors.affiliation: a Department of Anesthesiology and Pain Medicine, Gyeongsang National University Hospital, Jinju 660-702, Korea.
authors.forename: Hui-Jin
authors.initials: HJ
authors.lastname: Sung
authors.affiliation: a Department of Anesthesiology and Pain Medicine, Gyeongsang National University Hospital, Jinju 660-702, Korea.
authors.forename: Seong-Ho
authors.initials: SH
authors.lastname: Ok
authors.affiliation: b Department of Physiology, Kwandong University College of Medicine, Kangneung 201-701, Korea.
authors.forename: Seong-Chun
authors.initials: SC
authors.lastname: Kwon
authors.affiliation: a Department of Anesthesiology and Pain Medicine, Gyeongsang National University Hospital, Jinju 660-702, Korea.
authors.forename: Kwang Seong
authors.initials: KS
authors.lastname: Cheon
authors.affiliation: c Department of Pharmacology, Gyeongsang National University School of Medicine, Jinju 660-772, Korea.
authors.forename: Hye Jung
authors.initials: HJ
authors.lastname: Kim
authors.affiliation: c Department of Pharmacology, Gyeongsang National University School of Medicine, Jinju 660-772, Korea.
authors.forename: Ki Churl
authors.initials: KC
authors.lastname: Chang
authors.affiliation: d Department of Anesthesiology and Pain Medicine, Gyeongsang National University Hospital, Gyeongsang National University School of Medicine, Jinju 660-702, Korea.
authors.forename: Il-Woo
authors.initials: IW
authors.lastname: Shin
authors.affiliation: d Department of Anesthesiology and Pain Medicine, Gyeongsang National University Hospital, Gyeongsang National University School of Medicine, Jinju 660-702, Korea.
authors.forename: Heon-Keun
authors.initials: HK
authors.lastname: Lee
authors.affiliation: d Department of Anesthesiology and Pain Medicine, Gyeongsang National University Hospital, Gyeongsang National University School of Medicine, Jinju 660-702, Korea.
authors.forename: Young-Kyun
authors.initials: YK
authors.lastname: Chung
authors.affiliation: d Department of Anesthesiology and Pain Medicine, Gyeongsang National University Hospital, Gyeongsang National University School of Medicine, Jinju 660-702, Korea.|e Institute of Health Sciences, Gyeongsang National University School of Medicine, Jinju 660-702, Korea.
authors.forename: Ju-Tae
authors.initials: JT
authors.lastname: Sohn
mesh_terms: D058647:Adrenergic alpha-2 Receptor Agonists / Q000378:metabolism*; D000818:Animals; D001011:Aorta / Q000187:drug effects* / Q000378:metabolism; D002118:Calcium / Q000378:metabolism* / Q000493:pharmacokinetics; D002463:Cell Membrane Permeability / Q000187:drug effects*; D020927:Dexmedetomidine / Q000819:agonists / Q000378:metabolism* / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D011189:Potassium Chloride / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011941:Receptors, Adrenergic / Q000378:metabolism; D054460:rho-Associated Kinases / Q000378:metabolism
chemical_list: D058647:Adrenergic alpha-2 Receptor Agonists; D011941:Receptors, Adrenergic; D011189:Potassium Chloride; D020927:Dexmedetomidine; D019869:Phosphatidylinositol 3-Kinases; D054460:rho-Associated Kinases; D011493:Protein Kinase C; D002118:Calcium