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Contribution of endocannabinoids in the endothelial protection afforded by ischemic preconditioning in the isolated rat heart.

机译:内源性大麻素在离体大鼠心脏中通过缺血预处理提供的内皮保护作用。

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The aim of the present study was to assess the contribution of endogenous cannabinoids in the protective effect of ischemic preconditioning on the endothelial function in coronary arteries of the rat. Isolated rat hearts were exposed to a 30-min low flow ischemia (1 ml/min) followed by 20-min reperfusion, after which the response to the endothelium-dependent vasodilator, serotonine (5-HT), was compared with that of the endothelium-independent vasodilator, sodium nitroprusside (SNP). In untreated hearts, ischemia-reperfusion diminished selectively 5-HT-induced vasodilatation, compared with time-matched sham hearts, the vasodilatation to SNP being unaffected. A 5-min zero-flow preconditioning ischemia in untreated hearts preserved the vasodilatation produced by 5-HT. Blockade of either CB(1)-receptors with SR141716A or CB(2)-receptors with SR144528 abolished the protective effect of preconditioning on the 5-HT vasodilatation. Perfusion with either palmitoylethanolamide or 2-arachidonoylglycerol 15 min before and throughout the ischemia mimicked preconditioning inasmuch as it protected the endothelium in a similar fashion. This protection was blocked by SR144528 in both cases, whereas SR141716A only blocked the effect of PEA. The presence of CB(1) and CB(2)-receptors in isolated rat hearts was confirmed by Western blots. In conclusion, the data suggest that endogenous cannabinoids contribute to the endothelial protective effect of ischemic preconditioning in rat coronary arteries.
机译:本研究的目的是评估内源性大麻素在缺血预处理对大鼠冠状动脉内皮功能的保护作用中的作用。将离体的大鼠心脏暴露于30分钟的低流量缺血(1 ml / min),然后再灌注20分钟,然后将其对内皮依赖性血管扩张剂5-羟色胺(5-HT)的反应与内皮依赖性血管舒张药硝普钠(SNP)。在未治疗的心脏中,与时间匹配的假心脏相比,缺血-再灌注选择性地减少了5-HT诱导的血管舒张,SNP的血管舒张不受影响。在未经治疗的心脏中进行5分钟的零流量预处理缺血可保留5-HT产生的血管舒张。具有SR141716A的CB(1)受体或具有SR144528的CB(2)受体的阻滞消除了对5-HT血管舒张的预处理的保护作用。在缺血之前和整个缺血过程中,在15分钟前用棕榈酰乙醇酰胺或2-花生四烯酸甘油灌注可以模拟预处理,因为它以类似的方式保护了内皮。在两种情况下,此保护都被SR144528阻止,而SR141716A仅阻止了PEA的作用。 Western印迹证实了孤立的大鼠心脏中的CB(1)和CB(2)受体的存在。总之,数据表明内源性大麻素有助于缺血预处理对大鼠冠状动脉的内皮保护作用。

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