罗哌卡因对离体人脐动脉收缩性的影响及其机制

目的 研究不同浓度罗哌卡因对离体人脐动脉平滑肌的收缩作用,并分析其可能的机制.方法 采用离体脐动脉环灌流模型,用MedLab生物信号采集系统测定并记录血管的张力变化情况,观察累积浓度罗哌卡因对去内皮血管环的收缩效应,并同时观察细胞外Ca~(2+)"浓度、L-型Ca~(2+)通道阻滞剂维拉帕米、内质网三磷酸肌醇受体阻滞剂肝素和兰尼定受体阻滞剂钌红对罗哌卡因血管效应的影响.结果 罗哌卡因诱发剂量关联性双相脐血管反应:在低浓度(1.0×10~(-5)～1.0 × 10(~4)moL/L)时收缩张力逐渐升高,较高浓度(3.0×10~(-4)～3.0×10~(-3)mol/L)时收缩张力依次回落.在无钙液中罗哌卡因未能诱发脐动脉环收缩,而随细胞外液钙离子浓度增加较低浓度罗哌卡因致脐动脉收缩张力增加.维拉帕米可显著抑制罗哌卡因对脐动脉环的收缩反应,而维拉帕米+钌红、维拉帕米+肝索并不增加维拉帕米的抑制作用.结论 罗哌卡因可诱发离体人脐动脉剂量关联性双相收缩效应.细胞外Ca~(2+)通过L-型钙通道内流,而非肌质网Ca~(2+)释放,使细胞内Ca~(2+)]升高介导了罗哌卡因诱发的血管平滑肌收缩反应.

Effect and mechanism of ropivacaine on the isolated human umbilical artery

Objective To investigation the effect of ropivacaine on the contraction of the isolated human umbilical artery and the mechanisms involved. Methods Endothelium-denuded human umbilical artery rings obtained from healthy full-term paturients were prepared. Using isometric force transducers and a fluorometer, the effect of ropivacaine in cumulative concentration on the contraction response induced by KCl in the presence or absence of verapamil, or verapamil plus ruthenium red or verapamil plus heparin was observed. Furthermore, the effect of ropivacaine on the contraction response of the artery rings incubated in different concentrations of extracellular Ca~(2+) was also observed. Results Ropivacaine induced a dose-dependent biphasic contractile response of human umbilical artery rings; increasing at concentrations of 1.0 × 10~(-5) to 1.0 ×10~(-4) mol/Land decreasing from 3. 0 × 10~(-4) to 3.0×10~(-3) mol/L, which was inhibited by verapamil, or verapamil plus ruthenium red, or verapamil plus heparin. No difference was found between pre-treatment of verapamil, verapamil plus ruthenium red and verapamil plus heparin. Ropivacaine induced no contractile response in Ca~(2+) -free solution and a extracellular Ca~(2+) dose-dependent increasing contractile response(1.0 × 10~( -4) to 3.0 × 10 ~(-2)mol/L ). Conclusion Ropivacaine induced a dose-dependent biphasic contractile response of human umbilical artery rings. The increase in intracellular Ca~(2+) concentrations by the extracellular Ca~(2+) influx, not by the release from the sarcoplasmic reticulum, is involved in ropivacaine-induced vasoconstriction of human umbilical artery smooth muscle.