氢溴酸樟柳碱对离体大鼠颈总动脉的作用及机制研究
In vitro Effect and Mechanism of Anisodine Hydrobromide on Common Carotid Artery of Rats

中文摘要： 目的 观察氢溴酸樟柳碱对离体大鼠颈总动脉的作用及相关机制。 方法 麻醉大鼠后，分离得到大鼠颈总动脉并制成血管环，采用离体血管环实验，观察氢溴酸樟柳碱在1×10 -4~5×10 -3 mol·L -1浓度范围内对KCl、苯肾上腺素（PHE）预收缩的内皮完整及去内皮血管环的作用；并观察预孵一氧化氮合酶抑制剂左旋硝基精氨酸甲酯（L-NAME）、不同的钾离子通道抑制剂格列本脲（Gly）、4-氨基吡啶（4-AP）、四乙基氯化铵（TEA）、BaCl 2对氢溴酸樟柳碱舒张血管环作用的影响；以2×10 -3 mol·L -1氢溴酸樟柳碱预孵血管环，观察其对以细胞内、外钙为收缩剂的血管收缩的作用，并探讨其舒张血管的机制。 结果 氢溴酸樟柳碱在体外1×10 -4~5×10 -3 mol·L -1浓度范围内能浓度依赖性舒张KCl和PHE预收缩的血管环，对KCl预收缩的血管环最大舒张幅度（E max）为33.97%±11.53%，并在低浓度（1×10 -4~1×10 -3 mol·L -1）收缩血管（ P<0.01， P<0.05），对PHE预收缩的血管环的半数有效浓度为5.61（3.88，8.10） mmol·L -1，E max=47.93%±18.63%；对PHE预收缩的去内皮血管环，氢溴酸樟柳碱舒张血管的E max无明显变化；而L-NAME、Gly、4-AP、TEA、BaCl 2对氢溴酸樟柳碱舒张PHE预收缩的血管环均无明显作用；在无Ca 2+溶液中，2×10 -3 mol·L -1氢溴酸樟柳碱可以显著增强PHE引起的血管环短暂收缩（ P<0.01）。 结论 氢溴酸樟柳碱能够在低浓度收缩离体大鼠颈总动脉环，并能浓度依赖性地舒张离体大鼠颈总动脉环，对血管的张力具有双向作用，且其机制与非内皮依赖途径及促肌浆网内钙释放相关。
英文摘要： Objective To study the effect and mechanism of anisodine hydrobromide on common carotid artery of rats. Methods The common carotid artery of anesthetized rat was isolated and made into a vascular ring. Potassium chloride (KCl) or phenylephrine (PHE) precontracted rat common carotid artery was then treated by anisodine hydrobromide at a concentration range of 1×10 -4-5×10 -3 mol·L -1. The nitric oxide synthase inhibitor N ω-nitro-L-arginine methyl ester (L-NAME) or potsssium (K +) channels inhibitors Glyburide (Gly); 4-Aminopyridine (4-AP); Tetraethylammonium chloride (TEA) and BaCl 2 were used to study their influence on the anisodine hydrobromide-induced vasorelaxation. Intracellular or extracellular calcium (Ca 2+) was used as agonist to deterimine whether contractile response could be affected by anisodine hydrobromide at a concentration of 2×10 -3 mol·L -1. Results The constricted common carotid artery ring induced by KCl or PHE could be dilated by anisodine hydrobromide in a concentration range of 1×10 -4-5×10 -3 mol·L -1 in vitro. In common carotid artery rings precontracted by KCl, anisodine hydrobromide-induced maximal relaxation magnitude (E msx) was 33.97%±11.53%, and a vasoconstrictor function was observed in the concentration of 1×10 -4-1×10 -3 mol·L -1 ( P<0.01, P<0.05). By contrast, in aortic rings precontracted by PHE, anisodine hydrobromide-induced median effect concentration (EC 50) was 5.61 (3.88, 8.10) mmol·L -1, and E max was 47.93%±18.63%. Compared with the endothelial complete blood vessel ring, there was no significant change in the E max of anisodine hydrobromide in the de-endothelial common carotid ring pre-contracted by PHE. Moreover, the supplementation of nitric oxide synthase inhibitor L-NAME or K + channels inhibitors Gly, 4-AP, TEA and