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

作者：Kim Hee Jin; Sohn Ju Tae^*; Jeong Young Seok; Cho Man Seok; Kim Hye Jung; Chang Ki Churl; Shin Mi Kyung; Park Chang Shin; Chung Young Kyun

来源：CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, 2009, 36(4): 406-412.

DOI：10.1111/j.1440-1681.2008.05082.x

• cyclo-oxygenase pathway
• dexmedetomidine
• lipoxygenase pathway
• nitric oxide

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.

• 出版日期2009-4
• 单位河北医科大学