激肽在缺血预处理内皮保护作用中的角色。

Role of kinins in the endothelial protective effect of ischaemic preconditioning.

作者信息

Bouchard J F, Chouinard J, Lamontagne D

机构信息

Faculty of Pharmacy, Université de Montréal, Québec, Canada.

出版信息

Br J Pharmacol. 1998 Feb;123(3):413-20. doi: 10.1038/sj.bjp.0701619.

DOI:10.1038/sj.bjp.0701619

PMID:9504381

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1565180/

Abstract

The aim of this study was to assess whether the protective effect of ischaemic preconditioning on endothelial function in coronary arteries of the rat involves kinins. 2. Isolated hearts of the rat were exposed to a 30-min low-flow ischaemia (flow rate of 1 ml min[-1]) followed by 20-min reperfusion, after which coronaries were precontracted with 0.1 microM U-46619, and the response to the endothelium-dependent vasodilator, 5-hydroxytryptamine (5-HT, 10 microM), compared to that of the endothelium-independent vasodilator, sodium nitroprusside (SNP, 3 microM). 3. In untreated hearts, ischaemia-reperfusion diminished selectively 5-HT-induced vasodilatation, compared with time-matched sham hearts. The vasodilatation to SNP was unaffected after ischaemia-reperfusion. Preconditioning (5 min of zero-flow ischaemia followed by 10 min reperfusion) in untreated hearts preserved the vasodilatation produced by 5-HT. 4. Blockade of B1 and B2 receptors with either 3 nM [Lys[0], Leu8, des-Arg9]-bradykinin (LLDBK) or 10 nM Hoe 140 (icatibant), respectively, (started 15 min before ischaemic preconditioning or a corresponding sham period and stopped just before the 20-min reperfusion period) had no effect on the vasodilatation produced by either 5-HT or SNP in sham hearts. Pretreatment with Hoe 140 did not block the protective effect of ischaemic preconditioning on the 5-HT vasodilatation. In contrast, LLDBK halved the protective effect of ischaemic preconditioning on endothelium-dependent vasodilatation. 5. Perfusion with either bradykinin or des-Arg9-bradykinin (1 nM) 30 min before and lasting throughout the ischaemia protected the endothelium. 6. In conclusion, ischaemic preconditioning affords protection to the endothelial function in coronary resistance arteries of the rat partly by activation of B1 receptors. Although exogenous BK perfusion can protect the endothelium, B2 receptors do not play an important role in this protection in the rat isolated heart.

摘要

本研究的目的是评估缺血预处理对大鼠冠状动脉内皮功能的保护作用是否涉及激肽。2. 将大鼠离体心脏暴露于30分钟的低流量缺血（流速为1毫升/分钟），随后进行20分钟的再灌注，之后用0.1微摩尔/升的U - 46619使冠状动脉预收缩，并将对内皮依赖性血管舒张剂5 - 羟色胺（5 - HT，10微摩尔/升）的反应与对非内皮依赖性血管舒张剂硝普钠（SNP，3微摩尔/升）的反应进行比较。3. 与时间匹配的假手术心脏相比，在未经处理的心脏中，缺血再灌注选择性地减弱了5 - HT诱导的血管舒张。缺血再灌注后对SNP的血管舒张作用未受影响。未经处理的心脏进行预处理（零流量缺血5分钟，随后再灌注10分钟）可保留5 - HT产生的血管舒张作用。4. 分别用3纳摩尔的[赖氨酸[0]，亮氨酸8，去精氨酸9] - 缓激肽（LLDBK）或10纳摩尔的Hoe 140（艾替班特）阻断B1和B2受体（在缺血预处理或相应的假手术期前15分钟开始，在20分钟再灌注期前停止），对假手术心脏中5 - HT或SNP产生的血管舒张作用均无影响。用Hoe 140预处理并未阻断缺血预处理对5 - HT血管舒张的保护作用。相比之下，LLDBK使缺血预处理对内皮依赖性血管舒张的保护作用减半。5. 在缺血前30分钟灌注缓激肽或去精氨酸9 - 缓激肽（1纳摩尔）并持续至整个缺血期可保护内皮。6. 总之，缺血预处理部分通过激活B1受体为大鼠冠状动脉阻力血管的内皮功能提供保护。虽然外源性缓激肽灌注可保护内皮，但B2受体在大鼠离体心脏的这种保护中不发挥重要作用。