Timponi Clarisse F, Oliveira Nilton E, Arruda Roberia M P, Meyrelles Silvana S, Vasquez Elisardo C
Laboratory of Transgenes and Cardiovascular Control, Physiological Sciences Graduate Program, Biomedical Center, Federal University of Espirito Santo, Vitoria, ES, Brazil.
Basic Clin Pharmacol Toxicol. 2006 May;98(5):518-20. doi: 10.1111/j.1742-7843.2006.pto_397.x.
Previous clinical and experimental studies have indicated that ropivacaine, a local anaesthetic agent, exerts vasoconstrictor effects. In this study, the contractile effects of ropivacaine were investigated in vitro on mesenteric arteriolar beds obtained from 22 adult male C57BL/6J mice. The mesenteric arteriolar bed was perfused at constant rate (2 ml/min.) with oxygenated physiological salt solution using a roller pump. First we studied the effects of ropivacaine (3.2x10(-4) to 2.2x10(-2) mol/l) on the perfusion pressure and observed a dose-dependent pressor response, reaching a maximal increase of 26.0+/-3.7 mmHg. In a second study, we observed that after the mechanical removal of the endothelium ropivacaine-induced contractile responses were significantly reduced to a maximal of 13.5+/-0.7 mmHg. In a third set of experiments, we observed that under the effect of the cyclooxygenase inhibitor indomethacin (0.01 micromol/l) the ropivacaine-induced pressor response was significantly reduced to a maximal increase of 17.5+/-0.4 mmHg. This is the first evidence that this long-acting local anesthetic causes vasoconstriction in the perfused mesenteric arteriolar bed and that, at least in part, this effect is mediated by the endothelium since the cyclooxygenase inhibitor indomethacin reduced the ropivacaine-induced vasoconstriction to approximately 50%.
以往的临床和实验研究表明，局部麻醉药罗哌卡因具有血管收缩作用。在本研究中，我们对从22只成年雄性C57BL/6J小鼠获取的肠系膜小动脉床进行体外研究，以探讨罗哌卡因的收缩作用。使用滚轴泵以恒定速率（2毫升/分钟）用含氧生理盐溶液灌注肠系膜小动脉床。首先，我们研究了罗哌卡因（3.2×10⁻⁴至2.2×10⁻²摩尔/升）对灌注压力的影响，观察到剂量依赖性升压反应，最大增加幅度为26.0±3.7毫米汞柱。在第二项研究中，我们观察到在机械去除内皮后，罗哌卡因诱导的收缩反应显著降低至最大值13.5±0.7毫米汞柱。在第三组实验中，我们观察到在环氧化酶抑制剂吲哚美辛（0.01微摩尔/升）的作用下，罗哌卡因诱导的升压反应显著降低至最大增加幅度17.5±0.4毫米汞柱。这是首个证据表明这种长效局部麻醉药在灌注的肠系膜小动脉床中引起血管收缩，并且至少部分这种作用是由内皮介导的，因为环氧化酶抑制剂吲哚美辛将罗哌卡因诱导的血管收缩降低至约50%。
