Assessment of the effects of ropivacaine on vascular reactivity in rat mesenteric artery

INTRODUCTION: Ropivacaine (ROPI) is a local anesthetic of long duration of action, more recently introduced in medicine, however is not available for dental use in tubes yet. Clinical and animal studies have confirmed that bupivacaine is an effective anesthetic that also has an intrinsic vasoconstrictor effect.OBJECTIVE: To evaluate the effects of ropivacaine on vascular reactivity in isolated rat mesenteric artery, compare this to the effect of lidocaine (LIDO) and evaluate the possible involvement of the vascular endothelium induced by ROPI in isolated rat mesenteric artery ring response.MATERIAL AND METHOD: It was used 12 male Wistar rats (250-300g). The animals were euthanized and through an incision in the abdomen of the animal, the mesenteric artery was removed. Artery rings (1-2 mm) were obtained by the mesenteric artery, which were kept in vats containing 10 ml of Tyrode's nutrient solution kept at 37 °C and gassed with carbogen. For the recording of isometric contractions, each ring was suspended by cotton lines to a force transducer connected to a data acquisition system.RESULT: Both the LIDO as ROPI showed no vasoconstrictor effect on the basal tone of rings with functional endothelium. However, when the rings were precontracted with phenylephrine, both drugs were able to induce concentration-dependent vasorelaxation (Emax = 31.7 ± 3.3%, n = 6 for LIDO and 69 ± 8%, n = 6 for ROPI) that were not altered after removal of the endothelium (Emax= 28.7 ± 1.3%, n = 7 for LIDO and Emax = 58.8 ± 5.9%, n = 6 for ROPI). In rings without functional endothelium and precontracted with depolarizing Tyrode solution (80 mM KCl), the LIDO-induced vasorelaxation was no significantly changed (Emax = 29 ± 3%, n = 7). However, ROPI-induced vasorelaxation was reduced in this protocol and the presence of 1 mM tetraethylammonium (TEA) (Emax = 21.2 ± 5.1%, n = 7 and Emax = 17.4 ± 3.7, n = 4, respectively).CONCLUSION: ROPI produces vasorelaxant effect in rat superior mesenteric artery, which is independent of the participation of the endothelium. This effect seems to involve K+ channels in vascular smooth muscle cell.

引言：罗哌卡因（Ropivacaine, ROPI）是一种长效局部麻醉剂，近年才被应用于临床，但目前尚无适用于牙科的管状剂型上市。临床与动物实验均已证实，布比卡因是一种有效的麻醉药物，同时具备内在的血管收缩效应。
研究目的：评估罗哌卡因对离体大鼠肠系膜上动脉血管反应性的影响，并将其与利多卡因（lidocaine, LIDO）的作用进行比较，同时探究罗哌卡因诱导的血管内皮在离体大鼠肠系膜动脉环反应中的潜在参与作用。
材料与方法：选用12只雄性Wistar大鼠，体重250~300g。将大鼠实施安乐死后，通过腹部切口摘取其肠系膜动脉。将肠系膜动脉剪制成1~2mm的动脉环，置于装有10ml台氏营养液的器官浴槽中，维持温度37℃并持续通入碳混合气（carbogen）。为记录等长收缩反应，将每个动脉环通过棉线悬挂于连接数据采集系统的张力换能器上。
结果：在具备完整功能血管内皮的大鼠肠系膜上动脉环基础张力下，利多卡因与罗哌卡因均未表现出血管收缩效应。然而，当动脉环经苯肾上腺素预收缩后，两种药物均可诱导出浓度依赖性的血管舒张反应：利多卡因组最大舒张效应Emax=31.7±3.3%（n=6），罗哌卡因组Emax=69±8%（n=6）；去除血管内皮后，上述效应未发生明显改变，利多卡因组Emax=28.7±1.3%（n=7），罗哌卡因组Emax=58.8±5.9%（n=6）。在去除血管内皮且经80mM氯化钾去极化台氏液预收缩的动脉环中，利多卡因诱导的血管舒张反应无显著变化（Emax=29±3%，n=7）。但罗哌卡因诱导的血管舒张反应在该实验方案中被削弱，加入1mM四乙铵（tetraethylammonium, TEA）后，该反应进一步受到抑制，两组Emax分别为21.2±5.1%（n=7）与17.4±3.7%（n=4）。
结论：罗哌卡因可在大鼠肠系膜上动脉中产生血管舒张效应，该效应不依赖于血管内皮的参与，其作用机制似乎与血管平滑肌细胞上的钾离子通道有关。