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Mepivacaine-induced contraction is attenuated by endothelial nitric oxide release in isolated rat aorta

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Mepivacaine is an aminoamide-linked local anesthetic with an intermediate duration that intrinsically produces vasoconstriction both in vivo and in vitro. The aims of this in-vitro study were to examine the direct effect of mepivacaine in isolated rat aortic rings and to determine the associated cellular mechanism with a particular focus on endothelium-derived vasodilators, which modulate vascular tone. In the aortic rings with or without endothelium, cumulative mepivacaine concentration–response curves were generated in the presence or absence of the following antagonists: N ω-nitro-l-arginine methyl ester [l-NAME], indomethacin, fluconazole, methylene blue, 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one [ODQ], verapamil, and calcium-free Krebs solution. Mepivacaine produced vasoconstriction at low concentrations (1 × 10−3 and 3 × 10−3 mol/L) followed by vasodilation at a high concentration (1 × 10−2 mol/L). The mepivacaine-induced contraction was higher in endothelium-denuded aortae than in endothelium-intact aortae. Pretreatment with l-NAME, ODQ, and methylene blue enhanced mepivacaine-induced contraction in the endothelium-intact rings, whereas fluconazole had no effect. Indomethacin slightly attenuated mepivacaine-induced contraction, whereas verapamil and calcium-free Krebs solution more strongly attenuated this contraction. The vasoconstriction induced by mepivacaine is attenuated mainly by the endothelial nitric oxide – cyclic guanosine monophosphate pathway. In addition, mepivacaine-induced contraction involves cyclooxygenase pathway activation and extracellular calcium influx via voltage-operated calcium channels.
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Keywords: L-NAME; aorta; aorte; contraction; endothelium; endothelium-derived vasodilators; endothélium; l-NAME; mepivacaine; mépivacaïne; nitric oxide; oxyde nitrique; vasodilatateurs dérivés de l’endothélium

Document Type: Research Article

Affiliations: 1: Department of Anesthesiology, Charmjoeun Obstetrics and Gynecology Clinic, Jinju, Korea. 2: Department of Oral and Maxillofacial Surgery, Gyeongsang National University Hospital, Jinju, 660-702, Korea. 3: Department of Anesthesiology and Pain Medicine, Gyeongsang National University Hospital, Jinju, 660-702, Korea. 4: Department of Pharmacology, Gyeongsang National University School of Medicine, Jinju, 660-772, Korea. 5: Department of Anesthesiology and Pain Medicine, Gyeongsang National University Hospital, Gyeongsang National University School of Medicine, Jinju, 660-772, Korea.

Publication date: July 4, 2012

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