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 journalArticlepeer-review

15 Citations (Scopus)


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
Issue number4
Publication statusPublished - 2009 Apr
Externally publishedYes

ASJC Scopus subject areas

  • Anesthesiology and Pain Medicine


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