DIRECT EFFECT OF DEXMEDETOMIDINE ON RAT ISOLATED AORTA INVOLVES ENDOTHELIAL NITRIC OXIDE SYNTHESIS AND ACTIVATION OF THE LIPOXYGENASE PATHWAY

被引：24

作者：

Kim, Hee-Jin ^{[1
]}

Sohn, Ju-Tae ^{[1
,3
]}

Jeong, Young-Seok ^{[1
]}

Cho, Man Seok ^{[1
]}

Kim, Hye Jung ^{[2
,3
]}

Chang, Ki Churl ^{[2
,3
]}

Shin, Mi-Kyung ^{[4
]}

Park, Chang-Shin ^{[4
]}

Chung, Young-Kyun ^{[1
]}

机构：

[1] Gyeongsang Natl Univ, Sch Med, Dept Anaesthesiol & Pain Med, Jinju 660702, Gyeongnam, South Korea

[2] Gyeongsang Natl Univ, Sch Med, Dept Pharmacol, Jinju 660702, Gyeongnam, South Korea

[3] Gyeongsang Natl Univ, Sch Med, Inst Hlth Sci, Jinju 660702, Gyeongnam, South Korea

[4] Inha Univ, Coll Med,Project BK 21, Ctr Adv Med Educ,Dept Pharmacol, Inha Res Inst Med Sci,Med Toxicol Res Ctr, Inchon, South Korea

来源：

CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY | 2009年 / 36卷 / 04期

关键词：

cyclo-oxygenase pathway; dexmedetomidine; lipoxygenase pathway; nitric oxide; ALPHA(2)-ADRENOCEPTOR AGONISTS; HYPERPOLARIZING FACTOR; ALPHA-ADRENOCEPTORS; ARACHIDONIC-ACID; IN-VIVO; CONTRACTION; RELAXATION; RECEPTORS; REMOVAL; MUSCLE;

D O I：

10.1111/j.1440-1681.2008.05082.x

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

1. The aims of the present in vitro study were to examine the roles of pathways associated with arachidonic acid metabolism in dexmedetomidine-induced contraction and to determine which endothelium-derived vasodilators are involved in the endothelium-dependent attenuation of vasoconstriction elicited by dexmedetomidine. 2. Dexmedetomidine (10(-9)-10(-6) mol/L) concentration-response curves were constructed in: (i) aortic rings with no drug pretreatment; (ii) endothelium-denuded aortic rings pretreated with either 2 x 10(-5) mol/L quinacrine dihydrochloride, 10(-5) mol/L nordihydroguaiaretic acid (NDGA), 3 x 10(-5) mol/L indomethacin or 10(-5) mol/L fluconazole; and (iii) endothelium-intact aortic rings pretreated with either 5 x 10(-5) mol/L NG-nitro-L-arginine methyl ester (L-NAME), 10(-5) mol/L fluconazole, 10(-5) mol/L indomethacin, 10(-5) mol/L glibenclamide, 5 x 10(-3) mol/L tetraethylammonium or 5 x 10(-5) mol/L L-NAME plus rauwolscine (10(-5), 10(-6) mol/L). The production of nitric oxide ( NO) metabolites was determined in human umbilical vein endothelial cells treated with dexmedetomidine. 3. Quinacrine dihydrochloride, NDGA and indomethacin attenuated the dexmedetomidine-induced contraction of endothelium-denuded rings. Dexmedetomidine (10(-7)-10(-6) mol/L)induced contractions of endothelium-denuded rings were enhanced compared with those of endothelium-intact rings, as were dexmedetomidine-induced contractions of endothelium-intact rings pretreated with L-NAME or tetraethylammonium. Rauwolscine attenuated dexmedetomidine-induced contractions in endothelium-intact rings pretreated with L-NAME. Dexmedetomidine (10(-6) mol/L) was found to activate NO production. 4. Taken together, the results indicate that dexmedetomidine-induced contraction of aortic rings involves activation of the lipoxygenase and cyclo-oxygenase pathways and is attenuated by increased NO production following stimulation of endothelial. 2-adrenoceptors by dexmedetomidine.

引用

页码：406 / 412

页数：7

共 30 条

[1] Crucial role of NO and endothelium-derived hyperpolarizing factor in human sustained conduit artery flow-mediated dilatation [J].