Direct effect of ropivacaine involves lipoxygenase pathway activation in rat aortic smooth muscle

Hui Jin Sung, Ju Tae Sohn, Jae-Yong Park, Eun Mi Hwang, Ji Seok Baik, Koji Ogawa

Research output: Contribution to journalArticle

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Abstract

Purpose: Ropivacaine is a long-acting amino-amide local anesthetic that induces vasoconstriction in vitro and in vivo. The aim of this study was to investigate the pathways involved in arachidonic acid metabolism associated with S-ropivacaine-induced contraction of rat aortic smooth muscle in vitro. Methods: Rat thoracic aortic rings without endothelium were isolated and suspended for isometric tension recording. Cumulative dose-response curves were generated with concentrations of 10 -5 to 10 -3 M ropivacaine enantiomer in the presence or absence of quinacrine dihydrochloride, nordihydroguaiaretic acid, quinacrine dihydrochloride plus nordihydroguaiaretic acid, indomethacin, fluconazole, AA-861, and verapamil. The maximal S-ropivacaine-induced contractile response achieved at 3 × 10 -4 M was also assessed in aortic rings pretreated with normal or calcium-free Krebs solution. Results: Ropivacaine enantiomers induced dose-dependent biphasic contractions in aortic rings. S-ropivacaine (10 -4 , 3 × 10 -4 M) induced a stronger contraction than R-ropivacaine. Quinacrine dihydrochloride (2 × 10 -5 , 4 × 10 -5 M) attenuated the S-ropivacaine-induced biphasic contraction in a dose-dependent manner. Indomethacin (3 × 10 -5 , 6 × 10 -5 M), nordihydroguaiaretic acid (10 -5 M), and AA-861 (10 -5 M) also attenuated the S-ropivacaine-induced dose-dependent biphasic contraction, whereas fluconazole (3 × 10 -5 ) had no effect. Combined pretreatment with quinacrine dihydrochloride and nordihydroguaiaretic acid almost completely abolished the S-ropivacaine-induced contraction. S-ropivacaine-induced contractile responses were attenuated by verapamil (10 -5 M) and calcium-free Krebs solution. Conclusion: S-ropivacaine induces dose-dependent biphasic contractions in rat aortic smooth muscle through a mechanism requiring extracellular calcium that is mediated by activation of the lipoxygenase pathway and, to a lesser extent, the cyclooxygenase pathway.

Original languageEnglish
Pages (from-to)298-306
Number of pages9
JournalCanadian Journal of Anesthesia
Volume56
Issue number4
DOIs
Publication statusPublished - 2009 Apr 1
Externally publishedYes

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Lipoxygenase
Smooth Muscle
Masoprocol
Quinacrine
Fluconazole
Verapamil
Calcium
Indomethacin
ropivacaine
Prostaglandin-Endoperoxide Synthases
Local Anesthetics
Vasoconstriction
Arachidonic Acid
Amides
Endothelium
Thorax

ASJC Scopus subject areas

  • Anesthesiology and Pain Medicine

Cite this

Direct effect of ropivacaine involves lipoxygenase pathway activation in rat aortic smooth muscle. / Sung, Hui Jin; Sohn, Ju Tae; Park, Jae-Yong; Hwang, Eun Mi; Baik, Ji Seok; Ogawa, Koji.

In: Canadian Journal of Anesthesia, Vol. 56, No. 4, 01.04.2009, p. 298-306.

Research output: Contribution to journalArticle

Sung, Hui Jin ; Sohn, Ju Tae ; Park, Jae-Yong ; Hwang, Eun Mi ; Baik, Ji Seok ; Ogawa, Koji. / Direct effect of ropivacaine involves lipoxygenase pathway activation in rat aortic smooth muscle. In: Canadian Journal of Anesthesia. 2009 ; Vol. 56, No. 4. pp. 298-306.
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abstract = "Purpose: Ropivacaine is a long-acting amino-amide local anesthetic that induces vasoconstriction in vitro and in vivo. The aim of this study was to investigate the pathways involved in arachidonic acid metabolism associated with S-ropivacaine-induced contraction of rat aortic smooth muscle in vitro. Methods: Rat thoracic aortic rings without endothelium were isolated and suspended for isometric tension recording. Cumulative dose-response curves were generated with concentrations of 10 -5 to 10 -3 M ropivacaine enantiomer in the presence or absence of quinacrine dihydrochloride, nordihydroguaiaretic acid, quinacrine dihydrochloride plus nordihydroguaiaretic acid, indomethacin, fluconazole, AA-861, and verapamil. The maximal S-ropivacaine-induced contractile response achieved at 3 × 10 -4 M was also assessed in aortic rings pretreated with normal or calcium-free Krebs solution. Results: Ropivacaine enantiomers induced dose-dependent biphasic contractions in aortic rings. S-ropivacaine (10 -4 , 3 × 10 -4 M) induced a stronger contraction than R-ropivacaine. Quinacrine dihydrochloride (2 × 10 -5 , 4 × 10 -5 M) attenuated the S-ropivacaine-induced biphasic contraction in a dose-dependent manner. Indomethacin (3 × 10 -5 , 6 × 10 -5 M), nordihydroguaiaretic acid (10 -5 M), and AA-861 (10 -5 M) also attenuated the S-ropivacaine-induced dose-dependent biphasic contraction, whereas fluconazole (3 × 10 -5 ) had no effect. Combined pretreatment with quinacrine dihydrochloride and nordihydroguaiaretic acid almost completely abolished the S-ropivacaine-induced contraction. S-ropivacaine-induced contractile responses were attenuated by verapamil (10 -5 M) and calcium-free Krebs solution. Conclusion: S-ropivacaine induces dose-dependent biphasic contractions in rat aortic smooth muscle through a mechanism requiring extracellular calcium that is mediated by activation of the lipoxygenase pathway and, to a lesser extent, the cyclooxygenase pathway.",
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T1 - Direct effect of ropivacaine involves lipoxygenase pathway activation in rat aortic smooth muscle

AU - Sung, Hui Jin

AU - Sohn, Ju Tae

AU - Park, Jae-Yong

AU - Hwang, Eun Mi

AU - Baik, Ji Seok

AU - Ogawa, Koji

PY - 2009/4/1

Y1 - 2009/4/1

N2 - Purpose: Ropivacaine is a long-acting amino-amide local anesthetic that induces vasoconstriction in vitro and in vivo. The aim of this study was to investigate the pathways involved in arachidonic acid metabolism associated with S-ropivacaine-induced contraction of rat aortic smooth muscle in vitro. Methods: Rat thoracic aortic rings without endothelium were isolated and suspended for isometric tension recording. Cumulative dose-response curves were generated with concentrations of 10 -5 to 10 -3 M ropivacaine enantiomer in the presence or absence of quinacrine dihydrochloride, nordihydroguaiaretic acid, quinacrine dihydrochloride plus nordihydroguaiaretic acid, indomethacin, fluconazole, AA-861, and verapamil. The maximal S-ropivacaine-induced contractile response achieved at 3 × 10 -4 M was also assessed in aortic rings pretreated with normal or calcium-free Krebs solution. Results: Ropivacaine enantiomers induced dose-dependent biphasic contractions in aortic rings. S-ropivacaine (10 -4 , 3 × 10 -4 M) induced a stronger contraction than R-ropivacaine. Quinacrine dihydrochloride (2 × 10 -5 , 4 × 10 -5 M) attenuated the S-ropivacaine-induced biphasic contraction in a dose-dependent manner. Indomethacin (3 × 10 -5 , 6 × 10 -5 M), nordihydroguaiaretic acid (10 -5 M), and AA-861 (10 -5 M) also attenuated the S-ropivacaine-induced dose-dependent biphasic contraction, whereas fluconazole (3 × 10 -5 ) had no effect. Combined pretreatment with quinacrine dihydrochloride and nordihydroguaiaretic acid almost completely abolished the S-ropivacaine-induced contraction. S-ropivacaine-induced contractile responses were attenuated by verapamil (10 -5 M) and calcium-free Krebs solution. Conclusion: S-ropivacaine induces dose-dependent biphasic contractions in rat aortic smooth muscle through a mechanism requiring extracellular calcium that is mediated by activation of the lipoxygenase pathway and, to a lesser extent, the cyclooxygenase pathway.

AB - Purpose: Ropivacaine is a long-acting amino-amide local anesthetic that induces vasoconstriction in vitro and in vivo. The aim of this study was to investigate the pathways involved in arachidonic acid metabolism associated with S-ropivacaine-induced contraction of rat aortic smooth muscle in vitro. Methods: Rat thoracic aortic rings without endothelium were isolated and suspended for isometric tension recording. Cumulative dose-response curves were generated with concentrations of 10 -5 to 10 -3 M ropivacaine enantiomer in the presence or absence of quinacrine dihydrochloride, nordihydroguaiaretic acid, quinacrine dihydrochloride plus nordihydroguaiaretic acid, indomethacin, fluconazole, AA-861, and verapamil. The maximal S-ropivacaine-induced contractile response achieved at 3 × 10 -4 M was also assessed in aortic rings pretreated with normal or calcium-free Krebs solution. Results: Ropivacaine enantiomers induced dose-dependent biphasic contractions in aortic rings. S-ropivacaine (10 -4 , 3 × 10 -4 M) induced a stronger contraction than R-ropivacaine. Quinacrine dihydrochloride (2 × 10 -5 , 4 × 10 -5 M) attenuated the S-ropivacaine-induced biphasic contraction in a dose-dependent manner. Indomethacin (3 × 10 -5 , 6 × 10 -5 M), nordihydroguaiaretic acid (10 -5 M), and AA-861 (10 -5 M) also attenuated the S-ropivacaine-induced dose-dependent biphasic contraction, whereas fluconazole (3 × 10 -5 ) had no effect. Combined pretreatment with quinacrine dihydrochloride and nordihydroguaiaretic acid almost completely abolished the S-ropivacaine-induced contraction. S-ropivacaine-induced contractile responses were attenuated by verapamil (10 -5 M) and calcium-free Krebs solution. Conclusion: S-ropivacaine induces dose-dependent biphasic contractions in rat aortic smooth muscle through a mechanism requiring extracellular calcium that is mediated by activation of the lipoxygenase pathway and, to a lesser extent, the cyclooxygenase pathway.

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