TY - JOUR
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
N1 - Funding Information:
Financial support This study was supported in part by the invitation fellowship for research in Japan (2008) from the Japan Society for the Promotion of Science (JSPS).
PY - 2009/4
Y1 - 2009/4
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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U2 - 10.1007/s12630-009-9059-0
DO - 10.1007/s12630-009-9059-0
M3 - Article
C2 - 19296191
AN - SCOPUS:62949181078
VL - 56
SP - 298
EP - 306
JO - Canadian Journal of Anaesthesia
JF - Canadian Journal of Anaesthesia
SN - 0832-610X
IS - 4
ER -