摘要
目的观察阿魏酸硝酸酯类药物阿魏硝胺(FLNT)的血管舒张作用并探讨其可能机制。方法测定大鼠外周血管环(腔静脉、胸主动脉)张力,比较FLNT、硝酸甘油(NG)和硝酸异山梨酯(ISDN)对胸主动脉的舒张作用;观察鸟苷酸环化酶阻断剂亚甲蓝对FLNT血管舒张作用的影响以及FLNT对钾通道阻断剂(氯化钡、四乙胺、4-氨基吡啶和格列苯脲)血管张力的影响,研究FLNT对鸟苷酸环化酶和钾通道的作用。结果在大鼠内皮完整腔静脉,FLNT有浓度依赖性(1×10-7～1×10-4mol·L-1)舒张作用。在内皮完整及去内皮胸主动脉血管上,FLNT均浓度依赖性地降低去甲肾上腺素(NE)或高钾预收缩血管的张力,对内皮没有依赖性;FLNT使NE或高钾收缩曲线非平行右移,且使最大张力减小;FLNT对胸主动脉的舒张程度类似于ISDN。FLNT可以显著地对抗无钙环境下由NE引起的血管收缩。亚甲蓝能显著减弱FLNT的胸主动脉血管舒张作用,FLNT可显著地降低氯化钡和四乙胺的血管张力。结论FLNT对大鼠胸主动脉和腔静脉产生浓度依赖性舒张,其中胸主动脉产生舒张作用类似于硝酸异山梨酯,且为非内皮依赖性的。FLNT作用机制可能其与激活鸟苷酸环化酶,开放钾通道,抑制钙通道有关。
Abstract
OBJECTIVE To investigate the vasodilation effect and the possible mechanism of ferulaic nitrate(FLNT).METHODS The tensions of rat aorta artery and caval vein were measured.The comparison of vasorelaxation between FLNT and nitroglycerin(NG) or isosorbide dinitrate(ISDN) was made.And the blockers of guanylate cyclase(GC) and potassium channel were used to study the vasorelaxation mechanism of FLNT.RESULTS FLNT(1×10-7-1×10-4 mol·L-1) caused the concentration-dependent relaxation of rat caval vein and aorta artery.There is no significant difference between the endothelium-intact aorta rings and endothelium denuded aorta artery.In endothelium-intact aorta rings precontracted with norepinephrine(NE,1×10-6mol·L-1) or high level of K+(4×10-2 mol·L-1),FLNT relaxed almost the same degree as ISDN on aorta artery.FLNT caused unpaired shift of NE or KCl concentration-response curve to the right and decreased the maximum response.Without Ca2+,the contraction caused by NE was significantly inhibited by FLNT.The vessel tension of mythelene blue and some potassium channel blockers were reduced by FLNT on rat aorta rings.CONCLUSION FLNT induced concentration-dependent relaxation on rat aorta artery and caval vein.The relaxation of rat aorta was similar to isosorbide dinitrate and endothium-independent.The mechanism was possibly related to guanylate cyclase activation and potassium channel openening,and also possibly related to the inhibition of Ca2+ channel.
关键词
硝酸酯 /
血管舒张 /
鸟苷酸环化酶 /
钾通道
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Key words
nitrate /
vasodilation /
guanylate cyclase /
potassium channel
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王占庆;陈凯;王金萍;姜楠;曾明;许景峰.
阿魏硝胺的血管舒张作用与机制[J]. 中国药学杂志, 2008, 43(21): 1624-1628
WNG Zhn-qing;CHEN Ki;WNG Jin-ping;JING Nn;ZENG Ming;XU Jing-feng.
Vasodilation Effect of Ferulaic Nitrate and Its Mechanism [J]. Chinese Pharmaceutical Journal, 2008, 43(21): 1624-1628
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脚注
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基金
国家新药研究基金资助项目(96-901-05-243)
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