C-Jun NH2-Terminal Kinase Contributes to Dexmedetomidine-Induced Contraction in Isolated Rat Aortic Smooth Muscle.
10.3349/ymj.2011.52.3.420
- Author:
Seong Ho OK
1
;
Young Seok JEONG
;
Jae Gak KIM
;
Seung Min LEE
;
Hui Jin SUNG
;
Hye Jung KIM
;
Ki Churl CHANG
;
Seong Chun KWON
;
Ju Tae SOHN
Author Information
1. Department of Anesthesiology and Pain Medicine, Gyeongsang National University Hospital, Jinju, Korea.
- Publication Type:Original Article ; In Vitro ; Research Support, Non-U.S. Gov't
- Keywords:
Dexmedetomidine;
mitogen-activated protein kinase;
alpha2B-adrenoceptors;
hypertension;
rat aorta
- MeSH:
Adrenergic alpha-2 Receptor Agonists/*pharmacology;
Animals;
Anthracenes/pharmacology;
Aorta/cytology;
Dexmedetomidine/*pharmacology;
Enzyme Inhibitors/pharmacology;
Extracellular Signal-Regulated MAP Kinases/antagonists & inhibitors/physiology;
Flavonoids/pharmacology;
Imidazoles/pharmacology;
JNK Mitogen-Activated Protein Kinases/antagonists & inhibitors/*physiology;
Male;
*Muscle Contraction;
Muscle, Smooth, Vascular/drug effects/enzymology/*physiology;
Protein Isoforms/antagonists & inhibitors/physiology;
Pyridines/pharmacology;
Rats;
Rats, Sprague-Dawley;
p38 Mitogen-Activated Protein Kinases/antagonists & inhibitors/physiology
- From:Yonsei Medical Journal
2011;52(3):420-428
- CountryRepublic of Korea
- Language:English
-
Abstract:
PURPOSE: Dexmedetomidine, a full agonist of alpha2B-adrenoceptors, is used for analgesia and sedation in the intensive care units. Dexmedetomidine produces an initial transient hypertension due to the activation of post-junctional alpha2B-adrenoceptors on vascular smooth muscle cells (SMCs). The aims of this in vitro study were to identify mitogen-activated protein kinase (MAPK) isoforms that are primarily involved in full, alpha2B-adrenoceptor agonist, dexmedetomidine-induced contraction of isolated rat aortic SMCs. MATERIALS AND METHODS: Rat thoracic aortic rings without endothelium were isolated and suspended for isometric tension recording. Cumulative dexmedetomidine (10(-9) to 10(-6) M) dose-response curves were generated in the presence or absence of extracellular signal-regulated kinase (ERK) inhibitor PD 98059, p38 MAPK inhibitor SB 203580, c-Jun NH2-terminal kinase (JNK) inhibitor SP 600125, L-type calcium channel blocker (verapamil and nifedipine), and alpha2-adrenoceptor inhibitor atipamezole. Dexmedetomidine-induced phosphorylation of ERK, JNK, and p38 MAPK in rat aortic SMCs was detected using Western blotting. RESULTS: SP 600125 (10(-6) to 10(-5) M) attenuated dexmedetomidine-evoked contraction in a concentration-dependent manner, whereas PD 98059 had no effect on dexmedetomidine-induced contraction. SB 203580 (10(-5) M) attenuated dexmedetomidine-induced contraction. Dexmedetomidine-evoked contractions were both abolished by atipamezole and attenuated by verapamil and nifedipine. Dexmedetomidine induced phosphorylation of JNK and p38 MAPK in rat aortic SMCs, but did not induce phosphorylation of ERK. CONCLUSION: Dexmedetomidine-induced contraction involves a JNK- and p38 MAPK-mediated pathway downstream of alpha2-adrenoceptor stimulation in rat aortic SMCs. In addition, dexmedetomidine-induced contractions are primarily dependent on calcium influx via L-type calcium channels.
