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4. Mepivacaine-induced contraction involves phosphorylation of extracellular signal-regulated kinase through activation of the lipoxygenase pathway in isolated rat aortic smooth muscle

Author

Lee, Hyo Min, Ok, Seong-Ho, Sung, Hui-Jin, Eun, So Young, Kim, Hye Jung, Lee, Soo Hee, Kang, Sebin, Shin, Il-Woo, Lee, Heon Keun, Chung, Young-Kyun, Choi, Mun-Jeoung, Bae, Sung Il, and Sohn, Ju-Tae

Subjects
Physiological aspects, Research, Dosage and administration, Health aspects, Oxidases -- Physiological aspects -- Health aspects -- Research, Phosphorylation -- Research -- Physiological aspects -- Health aspects, Mepivacaine -- Dosage and administration -- Research, Phosphotransferases -- Physiological aspects -- Health aspects -- Research, Smooth muscle -- Physiological aspects -- Health aspects -- Research, Local anesthetics -- Dosage and administration -- Research, Cellular signal transduction -- Research -- Health aspects -- Physiological aspects, Aortic valve -- Physiological aspects -- Health aspects -- Research, Anesthetics -- Dosage and administration -- Research
Abstract

Introduction Mepivacaine is an aminoamide local anesthetic with an intermediate duration that intrinsically produces vasoconstriction both in vivo and in vitro (Willatts and Reynolds 1985; Wali 1986; Guinard et al. [...], Mepivacaine is an aminoamide local anesthetic with an intermediate duration that intrinsically produces vasoconstriction both in vivo and in vitro. This study investigated the arachidonic acid metabolic pathways involved in mepivacaine- induced contraction, and elucidated the associated cellular mechanism with a particular focus on extracellular signal-regulated kinase (ERK) in endothelium-denuded rat aorta. Isolated rat thoracic aortic rings were suspended for isometric tension recording. Cumulative mepivacaine concentration-response curves were generated in the presence or absence of the following inhibitors: quinacrine dihydrochloride, nordihydroguaiaretic acid, phenidone, AA-861, indomethacin, NS-398, SC-560, fluconazole, PD 98059, and verapamil. Mepivacaine-induced ERK phosphorylation, 5-lipoxygenase (5-LOX) expression, and cyclooxygenase (COX)-2 expression in rat aortic smooth muscle cells were detected by Western blot analysis in the presence or absence of inhibitors. Mepivacaine produced tonic contraction in isolated endothelium-denuded rat aorta. Quinacrine dihydrochloride, nordihydroguaiaretic acid, phenidone, AA-861, NS-398, PD 98059, and verapamil attenuated mepivacaine-induced contraction in a concentration-dependent manner. However, fluconazole had no effect on mepivacaine-induced contraction. PD 98059, quinacrine dihydrochloride, nordihydroguaiaretic acid, AA-861, phenidone, and indomethacin attenuated mepivacaine-induced ERK phosphorylation. Mepivacaine upregulated 5-LOX and COX-2 expression. These results suggest that mepivacaine-induced contraction involves ERK activation, which is primarily mediated by the 5-LOX pathway and in part by the COX-2 pathway. Key words: mepivacaine, vasoconstriction, extracellular signal-regulated kinase, lipoxygenase, aorta, cyclooxygenase, AA-861. La mepivacaine est un anesthesique local de la famille des aminoamides d'une duree intermediaire, qui produit intrinsequement une vasoconstriction tant in vivo que in vitro. Cette etude s'est penchee sur les voies metaboliques de l'acide arachidonique impliquees dans la contraction induite par la mepivacaine et a elucide le mecanisme cellulaire associe, en mettant l'emphase sur la kinase ERK (extracellular signal-regulated kinase) dans l'aorte de rat depourvue d'endothelium. Des anneaux aortiques thoraciques isoles ont ete mis en suspension pour l'enregistrement de la tension isometrique. Les courbes cumulatives de reponse en fonction de la concentration ont ete generees en presence ou en absence des inhibiteurs suivants : dihydrochlorure de quinacrine, acide nordihydroguaiaretique, phenidone, AA-861, indomethacine, NS-398, SC-560, fluconazole, PD 98059 et verapamil. La phosphorylation de ERK induite par la mepivacaine, l'expression de la 5-lipoxygenase (5-LOX) et l'expression de la cyclooxygenase (COX-2) dans les cellules musculaires lisses aortiques ont ete detectees par buvardage Western en presence ou en absence des inhibiteurs. La mepivacaine provoquait une contraction tonique de l'aorte de rat depourvue d'endothelium. Le dihydrochlorure de quinacrine, l'acide nordihydroguaiaretique, le phenidone, le AA-861, le NS-398, le PD 98059 et le verapamil attenuaient la contraction provoquee par la mepivacaine de maniere dependante de la concentration. Cependant, le fluconazole n'exercait pas d'effet sur la contraction induite par la mepivacaine. Le PD 98059, le dihydrochlorure de quinacrine, l'acide nordihydroguaiaretique, le AA-861, le phenidone et l'indomethacine attenuaient la phorphorylation de ERK induite par la mepivacaine. La mepivacaine regulait a la hause l'expression de 5-LOX et de COX-2. Ces resultats suggerent que la contraction provoquee par la mepivacaine implique l'activation de ERK principalement par l'intermediaire de la voie de 5-LOX et en partie par la voie de COX-2. [Traduit par la Redaction] Mots-cles : mepivacaine, vasoconstriction, ERK, lipoxygenase, aorte, cyclooxygenase, AA-861.

Published
2013
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8. Lipid Emulsion Attenuates Acetylcholine-Induced Relaxation in Isolated Rat Aorta

Author

Ok, Seong-Ho, primary, Lee, Soo Hee, additional, Yu, Jongsun, additional, Park, Jungchul, additional, Shin, Il-Woo, additional, Lee, Youngju, additional, Cho, Hyunhoo, additional, Choi, Mun-Jeoung, additional, Baik, Jiseok, additional, Hong, Jeong-Min, additional, Han, Jeong Yeol, additional, Lee, Heon Keun, additional, Chung, Young-Kyun, additional, and Sohn, Ju-Tae, additional

Published
2015
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11. Bupivacaine-induced Vasodilation Is Mediated by Decreased Calcium Sensitization in Isolated Endothelium-denuded Rat Aortas Precontracted with Phenylephrine

Author

Ok, Seong Ho, primary, Bae, Sung Il, additional, Kwon, Seong Chun, additional, Park, Jung Chul, additional, Kim, Woo Chan, additional, Park, Kyeong Eon, additional, Shin, Il Woo, additional, Lee, Heon Keun, additional, Chung, Young Kyun, additional, Choi, Mun Jeoung, additional, and Sohn, Ju Tae, additional

Published
2014
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12. Human Umbilical Cord Blood-Derived CD34-Positive Endothelial Progenitor Cells Stimulate Osteoblastic Differentiation of Cultured Human Periosteal-Derived Osteoblasts

Author

Lee, Jin-Ho, primary, Hah, Young-Sool, additional, Cho, Hee-Young, additional, Kim, Jin-Hyun, additional, Oh, Se-Heang, additional, Park, Bong-Wook, additional, Kang, Young-Hoon, additional, Choi, Mun-Jeoung, additional, Shin, Jeong-Kyu, additional, Rho, Gyu-Jin, additional, Jeon, Ryoung-Hoon, additional, Lee, Hee-Chun, additional, Kim, Gyoo-Cheon, additional, Kim, Uk-Kyu, additional, Kim, Jong-Ryoul, additional, Lee, Chang-Il, additional, and Byun, June-Ho, additional

Published
2014
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20. Vasoconstriction Potency Induced by Aminoamide Local Anesthetics Correlates with Lipid Solubility

Author

Sung, Hui-Jin, primary, Ok, Seong-Ho, additional, Sohn, Jin-Young, additional, Son, Yong Hyeok, additional, Kim, Jun Kyu, additional, Lee, Soo Hee, additional, Han, Jeong Yeol, additional, Lim, Dong Hoon, additional, Shin, Il-Woo, additional, Lee, Heon-Keun, additional, Chung, Young-Kyun, additional, Choi, Mun-Jeoung, additional, and Sohn, Ju-Tae, additional

Published
2012
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22. Vasoconstriction Potency Induced by Aminoamide Local Anesthetics Correlates with Lipid Solubility

Author

Sung, Hui-Jin, Ok, Seong-Ho, Sohn, Jin-Young, Hyeok Son, Yong, Kyu Kim, Jun, Hee Lee, Soo, Yeol Han, Jeong, Hoon Lim, Dong, Shin, Il-Woo, Lee, Heon-Keun, Chung, Young-Kyun, Choi, Mun-Jeoung, and Sohn, Ju-Tae

Abstract

Aminoamide local anesthetics induce vasoconstriction in vivo and in vitro. The goals of this in vitro study were to investigate the potency of local anesthetic-induced vasoconstriction and to identify the physicochemical property (octanol/buffer partition coefficient, pKa, molecular weight, or potency) of local anesthetics that determines their potency in inducing isolated rat aortic ring contraction. Cumulative concentration-response curves to local anesthetics (levobupivacaine, ropivacaine, lidocaine, and mepivacaine) were obtained from isolated rat aorta. Regression analyses were performed to determine the relationship between the reported physicochemical properties of local anesthetics and the local anesthetic concentration that produced 50% (ED50) of the local anesthetic-induced maximum vasoconstriction. We determined the order of potency (ED50) of vasoconstriction among local anesthetics to be levobupivacaine > ropivacaine > lidocaine > mepivacaine. The relative importance of the independent variables that affect the vasoconstriction potency is octanol/buffer partition coefficient > potency > pKa > molecular weight. The ED50 in endothelium-denuded aorta negatively correlated with the octanol/buffer partition coefficient of local anesthetics (r2=0.9563; P<0.001). The potency of the vasoconstriction in the endothelium-denuded aorta induced by local anesthetics is determined primarily by lipid solubility and, in part, by other physicochemical properties including potency and pKa.

Published
2012
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