Bouchard J F, Chouinard J, Lamontagne D
Facultésde pharmacie, Université de Montréal, Québec, Canada.
Arch Mal Coeur Vaiss. 1998 Aug;91(8):941-5.
The aim of this study was to assess whether the cardioprotective effect of ischaemic preconditioning (IPC) on endothelial function in resistance coronary arteries of the rat involves activation of kinin receptors. Isolated rat hearts perfused under constant flow conditions were exposed to 30 min of partial ischaemia (flow rate 1 mL/min) followed by 20 min of reperfusion. Preconditioning was performed with 5 min zero-flow ischaemia and 10 min reperfusion before the 30-min ischaemia. After the 20-min reperfusion period, coronaries were precontracted with U-46619 0.1 microM, and the coronary response to the endothelium-dependent vasodilator, serotonin (5-HT, 10 microM), was compared to that of the endothelium-independent vasodilator, sodium nitroprusside (SNP, 3 microM). Kinin B1 and B2 receptors were blocked with perfusion of either [Lys0, Leu8, des-Arg0]-Bradykinin 30nM (LLDBK) or Hoe 140 10 nM (Hoe) respectively, started 15 min before IPC or a corresponding sham period and stopped just before the 20-min reperfusion period. In untreated hearts, ischemia diminished selectively 5-HT-induced vasodilatation, compared to sham hearts (without ischaemia). The vasodilatation by SNP was unaffected after ischaemia and reperfusion. Preconditioning in untreated hearts preserved the vasodilatation produced by 5-HT. Treatment of hearts with either Hoe or LLDBK had no effect on the vasodilatation produced by both 5-HT and SNP in sham hearts. Pre-treatment with Hoe did not block the protective effect of IPC on the 5-HT vasodilatation. LLDBK halved the protective effect of IPC on endothelium-dependent vasodilatation. In addition, the protective effect of BK on the endothelial function in the isolated rat heart was blocked by LLDBK. These results suggest that IPC and exogenous kinin perfusions afford protection to endothelial function in resistance coronary arteries of the rat partially by activation of B1 kinin receptors. B2 receptors do not play any role in that protection.
本研究旨在评估缺血预处理（IPC）对大鼠阻力冠状动脉内皮功能的心脏保护作用是否涉及激肽受体的激活。在恒流条件下灌注的离体大鼠心脏先经历30分钟的部分缺血（流速1毫升/分钟），随后再灌注20分钟。预处理是在30分钟缺血之前进行5分钟的零流量缺血和10分钟的再灌注。在20分钟再灌注期后，冠状动脉用0.1微摩尔的U-46619进行预收缩，然后将冠状动脉对内皮依赖性血管舒张剂5-羟色胺（5-HT，10微摩尔）的反应与对内皮非依赖性血管舒张剂硝普钠（SNP，3微摩尔）的反应进行比较。分别在IPC或相应假手术期前15分钟开始灌注30纳摩尔的[Lys0, Leu8, des-Arg0]-缓激肽（LLDBK）或10纳摩尔的Hoe 140（Hoe）来阻断激肽B1和B2受体，灌注在20分钟再灌注期前结束。在未经处理的心脏中，与假手术心脏（无缺血）相比，缺血选择性地减弱了5-HT诱导的血管舒张。缺血和再灌注后，SNP引起的血管舒张不受影响。未经处理的心脏进行预处理可保留5-HT产生的血管舒张。用Hoe或LLDBK处理心脏对假手术心脏中5-HT和SNP产生的血管舒张均无影响。用Hoe预处理并未阻断IPC对5-HT血管舒张的保护作用。LLDBK使IPC对内皮依赖性血管舒张的保护作用减半。此外，LLDBK阻断了缓激肽对离体大鼠心脏内皮功能的保护作用。这些结果表明，IPC和外源性激肽灌注部分通过激活B1激肽受体为大鼠阻力冠状动脉的内皮功能提供保护。B2受体在该保护作用中不发挥任何作用。
