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.
ASJC Scopus subject areas
- Anesthesiology and Pain Medicine