Lin P L, Huang H H, Fan S Z, Tsai M C, Lin C H, Huang C H
Department of Pharmacology, College of Medicine, National Taiwan University, Taipei, Taiwan.
Acta Anaesthesiol Scand. 2007 Nov;51(10):1388-93. doi: 10.1111/j.1399-6576.2007.01443.x.
Previous studies have shown that ropivacaine has biphasic vascular effects, causing vasoconstriction at low concentrations and vasorelaxation at high concentrations. This study was designed to examine the role of the endothelium during accidental intravascular absorption of ropivacaine, and to elucidate the mechanisms responsible.
Isolated guinea pig aortic rings were suspended for isometric tension recording. The effects of ropivacaine on endothelium-intact and endothelium-denuded aortic rings were assessed. Endothelium-intact aortic rings were pre-contracted with phenylephrine before being exposed to ropivacaine and acetylcholine, in order to generate and compare concentration-response curves. In the absence and presence of yohimbine, propranolol, atropine, indometacin, N(G)-nitro-l-arginine methyl ester (l-NAME), 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) or methylene blue, the contractile response induced by ropivacaine was assessed on endothelium-intact aortic rings pre-contracted with phenylephrine.
Ropivacaine (3 x 10(-4) to 10(-2) mol/l) produced vasoconstriction in endothelium-denuded aortic rings, whereas no such response was observed in aortic rings with intact endothelium. In phenylephrine pre-contracted intact aortic rings, ropivacaine induced a greater degree of vasorelaxation than did acetylcholine. Yohimbine, propranolol and atropine all failed to affect the relaxation responses induced by ropivacaine. However, pre-treatment with indometacin (cyclo-oxygenase inhibitor), l-NAME (nitric oxide synthase inhibitor), methylene blue (soluble guanylyl cyclase inhibitor) or ODQ (soluble guanylyl cyclase inhibitor), significantly decreased the ropivacaine-induced relaxation of endothelium-intact aortic rings (3 x 10(-4) to 10(-2) mol/l).
Ropivacaine elicits an endothelium-dependent vasorelaxation in phenylephrine pre-contracted aortic rings via the nitric oxide-cyclic guanosine 3',5'-monophosphate pathway and the prostaglandin system.
先前的研究表明，罗哌卡因具有双相血管效应，在低浓度时引起血管收缩，在高浓度时引起血管舒张。本研究旨在探讨内皮在罗哌卡因意外血管内吸收过程中的作用，并阐明其机制。
将分离的豚鼠主动脉环悬挂起来进行等长张力记录。评估罗哌卡因对内皮完整和内皮剥脱的主动脉环的影响。在内皮完整的主动脉环中，先用去氧肾上腺素预收缩，然后再暴露于罗哌卡因和乙酰胆碱，以生成并比较浓度-反应曲线。在不存在和存在育亨宾、普萘洛尔、阿托品、吲哚美辛、N(G)-硝基-L-精氨酸甲酯（L-NAME）、1H-[1,2,4]恶二唑并[4,3-a]喹喔啉-1-酮（ODQ）或亚甲蓝的情况下，评估罗哌卡因对用去氧肾上腺素预收缩的内皮完整主动脉环诱导的收缩反应。
罗哌卡因（3×10(-4)至10(-2)mol/L）在去内皮的主动脉环中引起血管收缩，而在内皮完整的主动脉环中未观察到这种反应。在用去氧肾上腺素预收缩的完整主动脉环中，罗哌卡因比乙酰胆碱诱导更大程度的血管舒张。育亨宾、普萘洛尔和阿托品均未能影响罗哌卡因诱导的舒张反应。然而，用吲哚美辛（环氧化酶抑制剂）、L-NAME（一氧化氮合酶抑制剂）、亚甲蓝（可溶性鸟苷酸环化酶抑制剂）或ODQ（可溶性鸟苷酸环化酶抑制剂）预处理，显著降低了罗哌卡因对内皮完整主动脉环（3×10(-4)至10(-2)mol/L）诱导的舒张作用。
罗哌卡因通过一氧化氮-环鸟苷酸3',5'-单磷酸途径和前列腺素系统，在去氧肾上腺素预收缩的主动脉环中引发内皮依赖性血管舒张。
