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杜仲树皮提取物诱导的内皮依赖性血管舒张是由小血管中的一氧化氮(NO)和内皮衍生超极化因子(EDHF)介导的。

Endothelium-dependent vascular relaxation induced by Eucommia ulmoides Oliv. bark extract is mediated by NO and EDHF in small vessels.

作者信息

Kwan Chiu-Yin, Zhang Wen-Bo, Deyama Takeshi, Nishibe Sansei

机构信息

HSC-4N40, Department of Medicine, Faculty of Health Sciences, McMaster University, 1200 Main Street West, L8N 3Z5, Hamilton, Ontario, Canada.

出版信息

Naunyn Schmiedebergs Arch Pharmacol. 2004 Feb;369(2):206-11. doi: 10.1007/s00210-003-0822-4. Epub 2003 Dec 13.

Abstract

The vasorelaxant effects of the aqueous extract prepared from the bark of the Chinese medicinal herb, Eucommia ulmoides Oliv. (also referred to as Tu-Chung or Du-Zhong), which is a common active ingredient in traditional antihypertensive herbal prescriptions in China, have recently been characterized in rat aorta and dog carotid artery. The vasorelaxant effect of eucommia bark extract on these large elastic arteries was found to be entirely endothelium-dependent and nitric oxide (NO)-mediated. Since smaller muscular arteries play a more dominant role in the change of peripheral resistance and thus the regulation of blood pressure, we have now compared the relaxant effects of eucommia bark extract using aorta and the proximal as well as the distal ends of the superior mesenteric arteries from the rat, with a specific objective to investigate whether smaller muscular arteries also elicit endothelium-dependent vascular relaxation (EDVR) in response to eucommia bark extract. We have also determined whether the EDVR, if indeed occurring in the mesenteric arteries, is mediated entirely by NO, or whether it also involves endothelium-derived hyperpolarizing factor (EDHF). We found that all three types of vessel preparations elicit EDVR in response to the eucommia bark extract concentration-dependently in a similar manner to the relaxant responses to carbachol (CCh). Although the NO synthase inhibitor L-NAME totally abolished the EDVR in aorta, it only partial abolished EDVR in mesenteric arteries isolated from each end, the distal end being more resistant to L-NAME. However, the residual L-NAME-resistant relaxation of the rat mesenteric arteries could be further inhibited by preincubation of the vessels with the combination of L-NAME and 15-20 mM KCl (KCl itself at this low concentration caused little or no contraction). Therefore, the EDVR induced by the eucommia extract and CCh in aorta is mediated entirely by NO, and that in mesenteric arteries by NO as well as EDHF, with the EDHF component (inhibited by KCl) larger in the smaller distal end of the rat mesenteric artery. Results of our study offer a plausible mechanistic basis for the vasorelaxing action of Eucommia ulmoides Oliv., which may account for its well-documented antihypertensive action.

摘要

杜仲(Eucommia ulmoides Oliv.,在中国传统降压草药方中是一种常见的活性成分,也被称为杜仲皮或杜仲)树皮制备的水提取物的血管舒张作用,最近已在大鼠主动脉和犬颈动脉中得到表征。杜仲树皮提取物对这些大弹性动脉的血管舒张作用被发现完全依赖于内皮细胞且由一氧化氮(NO)介导。由于较小的肌性动脉在周围阻力变化以及血压调节中起更主要的作用,我们现在比较了杜仲树皮提取物对大鼠主动脉、肠系膜上动脉近端和远端的舒张作用,具体目的是研究较小的肌性动脉是否也会对杜仲树皮提取物产生内皮依赖性血管舒张(EDVR)。我们还确定了如果肠系膜动脉中确实发生EDVR,它是否完全由NO介导,或者是否还涉及内皮衍生的超极化因子(EDHF)。我们发现,所有三种血管制剂对杜仲树皮提取物均以浓度依赖性方式引发EDVR,其方式与对卡巴胆碱(CCh)的舒张反应相似。虽然NO合酶抑制剂L-NAME完全消除了主动脉中的EDVR,但它仅部分消除了从两端分离的肠系膜动脉中的EDVR,远端对L-NAME更具抗性。然而,大鼠肠系膜动脉中对L-NAME有抗性的残余舒张作用可通过将血管与L-NAME和15 - 20 mM氯化钾(KCl本身在此低浓度下几乎不引起收缩或不引起收缩)预孵育而进一步受到抑制。因此,杜仲提取物和CCh在主动脉中诱导的EDVR完全由NO介导,而在肠系膜动脉中由NO以及EDHF介导,在大鼠肠系膜动脉较小的远端,EDHF成分(被KCl抑制)更大。我们的研究结果为杜仲的血管舒张作用提供了一个合理的机制基础,这可能解释了其有充分记录的降压作用。

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