DIRECT EFFECT OF DEXMEDETOMIDINE ON RAT ISOLATED AORTA INVOLVES ENDOTHELIAL NITRIC OXIDE SYNTHESIS AND ACTIVATION OF THE LIPOXYGENASE PATHWAY |
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| Authors: | Hee-Jin Kim Ju-Tae Sohn Young-Seok Jeong Man Seok Cho Hye Jung Kim Ki Churl Chang Mi-Kyung Shin Chang-Shin Park Young-Kyun Chung |
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| Institution: | Department of Anaesthesiology and Pain Medicine,;Department of Pharmacology,;Institute of Health Sciences, Gyeongsang National University School of Medicine, Jinju, Gyeongnam and;Department of Pharmacology, Medicinal Toxicology Research Center, Inha Research Institute for Medical Sciences, Center for Advanced Medical Education, Inha University College of Medicine by BK-21 Project, Incheon, Republic of Korea |
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| Abstract: | - 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 × 10?5 mol/L quinacrine dihydrochloride, 10?5 mol/L nordihydroguaiaretic acid (NDGA), 3 × 10?5 mol/L indomethacin or 10?5 mol/L fluconazole; and (iii) endothelium‐intact aortic rings pretreated with either 5 × 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 × 10?3 mol/L tetraethylammonium or 5 × 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 α2‐adrenoceptors by dexmedetomidine.
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| Keywords: | cyclo-oxygenase pathway dexmedetomidine lipoxygenase pathway nitric oxide |
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