Dexmedetomidine-Induced Contraction in the Isolated Endothelium-Denuded Rat Aorta Involves PKC-dmediated JNK Phosphorylation

被引：9

作者：

Yu, Jongsun ^{[1
,2
]}

Ok, Seong-Ho ^{[1
,2
]}

Kim, Won Ho ^{[3
]}

Cho, Hyunhoo ^{[4
]}

Park, Jungchul ^{[4
]}

Shin, Il-Woo ^{[1
,2
]}

Lee, Heon Keun ^{[1
,2
]}

Chung, Young-Kyun ^{[1
,2
]}

Choi, Mun-Jeoung ^{[5
]}

Kwon, Seong-Chun ^{[6
]}

Sohn, Ju-Tae ^{[1
,2
,7
]}

机构：

[1] Gyeongsang Natl Univ, Sch Med, Dept Anesthesiol & Pain Med, Jinju Si 52727, South Korea

[2] Gyeongsang Natl Univ Hosp, Jinju Si 52727, South Korea

[3] Sungkyunkwan Univ, Sch Med, Samsung Changwon Hosp, Dept Anesthesiol & Pain Med, Chang Won, South Korea

[4] Gyeongsang Natl Univ Hosp, Dept Anesthesiol & Pain Med, Jinju, South Korea

[5] Gyeongsang Natl Univ Hosp, Dept Oral & Maxillofacial Surg, Jinju, South Korea

[6] Catholic Kwandong Univ, Coll Med, Inst Clin & Translat Res, Dept Physiol, Kangnung 25601, South Korea

[7] Gyeongsang Natl Univ, Inst Hlth Sci, Jinju, South Korea

来源：

INTERNATIONAL JOURNAL OF MEDICAL SCIENCES | 2015年 / 12卷 / 09期

基金：

新加坡国家研究基金会;

关键词：

dexmedetomidine; protein kinase C; aorta; protein kinase C-delta; vasoconstriction; c-Jun NH2-terminal kinase; PROTEIN-KINASE-C; SMOOTH-MUSCLE-CELLS; CORONARY HEMODYNAMICS; ACTIVATION; HYPERTENSION; AGONIST; VASOCONSTRICTION; COMPLICATIONS; MEDETOMIDINE; SEDATION;

D O I：

10.7150/ijms.11952

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Vasoconstriction mediated by the highly selective alpha-2 adrenoceptor agonist dexmedetomidine leads to transiently increased blood pressure and severe hypertension. The dexmedetomidine-induced contraction involves the protein kinase C (PKC)-mediated pathway. However, the main PKC isoform involved in the dexmedetomidine-induced contraction remains unknown. The goal of this in vitro study was to examine the specific PKC isoform that contributes to the dexmedetomidine-induced contraction in the isolated rat aorta. The endothelium-denuded rat aorta was suspended for isometric tension recording. Dexmedetomidine dose-response curves were generated in the presence or absence of the following inhibitors: the pan-PKC inhibitor, chelerythrine; the PKC-alpha and -beta inhibitor, Go6976; the PKC-alpha inhibitor, safingol; the PKC-beta inhibitor, ruboxistaurin; the PKC-delta inhibitor, rottlerin; the c-Jun NH2-terminal kinase (JNK) inhibitor, SP600125; and the myosin light chain kinase inhibitor, ML-7 hydrochloride. Western blot analysis was used to examine the effect of rottlerin on dexmedetomidine-induced PKC-delta expression and JNK phosphorylation in rat aortic vascular smooth muscle cells (VSMCs) and to investigate the effect of dexmedetomidine on PKC-delta expression in VSMCs transfected with PKC-delta small interfering RNA (siRNA) or control siRNA. Chelerythrine as well as SP600125 and ML-7 hydrochloride attenuated the dexmedetomidine-induced contraction. Go6976, safingol, and ruboxistaurin had no effect on the dexmedetomidine-induced contraction, whereas rottlerin inhibited the dexmedetomidine-induced contraction. Dexmedetomidine induced PKC-delta expression, whereas rottlerin and PKC-delta siRNA transfection inhibited dexmedetomidine-induced PKC-delta expression. Dexmedetomidine also induced JNK phosphorylation, which was inhibited by rottlerin. Taken together, these results suggest that the dexmedetomidine-induced contraction involves PKC-delta-dependent JNK phosphorylation in the isolated rat aorta.

引用

页码：727 / 736

页数：10

共 34 条

[31] Severe hypertension and bradycardia after dexmedetomidine for radiology sedation in a patient with acute transverse myelitis [J].