欧前胡素衍生物OW1对血管舒张作用及机制研究

Vasodilatation Effects and Mechanism of Imperatorin Derivative OW1

目的考察欧前胡素衍生物OW1对大鼠不同动脉的舒张作用,并探讨其可能的舒张作用机制。方法采用多通道微血管张力测定方法,以高钾预收缩的大鼠主动脉、肾动脉、大脑中动脉、冠状动脉、肺动脉以及肠系膜动脉,评价OW1对这6种动脉的舒张效应;分别考察内皮、β-肾上腺素受体、3种钾离子通道考察其对OW1舒张曲线的影响;干预细胞内钙及外钙的浓度,检测其对OW1抑制收缩曲线的影响。结果 OW1可以完全舒张上述6种动脉,E_(max)均在90%以上,p EC_(50)分别为(6. 11±0. 09),(5. 76±0. 01),(6. 22±0. 08),(5. 78±0. 05),(5. 65±0. 01)和(6. 59±0. 07)。阻断内皮、β-肾上腺素受体、ATP敏感性钾通道和内向整流钾通道后均对OW1的舒张曲线无影响,阻断钙离子激活钾离子通道可使OW1的舒张曲线明显地非平行性右移,E_(max)降低,并且OW1可以抑制外钙的内流以及内钙的释放,降低细胞内的钙离子浓度,从而抑制血管收缩。结论 OW1可以舒张上述6种血管,其涉及的血管舒张机制主要包括抑制电压依赖性钙通道和受体介导的Ca^(2+)的内流和释放。

OBJECTIVE To investigate vasodilation effect and mechanism of OW1 was investigated on rat aorta, renal artery, cerebral middle artery, coronary artery, pulmonary artery and mesenteric artery. METHODS Isometric tension was measured in a 610 M-DMT Wire Myograph System. 60 mmol·L-1 KCl was added to the baths to induce pre-contraction of the 6 arteries. The concentration-response curves of OW1 were constructed on endothelium-denuded aorta rings or blocking endothelial, beta adrenergic receptor, three potassium channels and changing the concentration of intracellular or external calcium respectively. RESULTS OW1 could relax the 6 arteries completely, and Emax were all above 95%. pEC50 were (6.11±0.09), (5.76±0.01), (6.22±0.08), (5.78±0.05), (5.65±0.01), and (6.59±0.07) respectively. β-Adrenoceptor, ATP sensitive potassium channel and inwardly rectifying potassium channel were not involved in the vasodilatation, whereas blockage of calcium-activated potassium channel with tetraethylammonium had effect. OW1 could inhibit the influx of extracellular calcium and the release of intracellular calcium, thereby inhibiting vasoconstriction. CONCLUSION OW1 could relax the six arteries. The possible mechanisms of the vasodilatation are mainly involved with inhibiting voltage dependent calcium channel and receptor-mediated Ca2+ influx and release, and might be partly due to opening calcium-activated potassium channel.