Bouchard J F, Chouinard J, Lamontagne D
Faculty of Pharmacy, University of Montreal, Quebec, Canada.
Cardiovasc Res. 2000 Jan 14;45(2):418-27. doi: 10.1016/s0008-6363(99)00343-0.
To assess whether the protective effect of ischaemic preconditioning (IPC) on endothelial function in coronary arteries of the rat involves prostaglandins.
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, after which 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). Prostaglandin production was blocked with a perfusion of indomethacin 10 microM started 15 min before IPC or a corresponding sham period and stopped just before the 20-min reperfusion period.
In untreated hearts, ischaemia diminished selectively 5-HT-induced vasodilatation, compared to sham hearts. The vasodilatation by SNP was unaffected after ischaemia and reperfusion. IPC (5 min of zero-flow ischaemia followed by 10 min reperfusion before the 30-min partial ischaemia) preserved the vasodilatation produced by 5-HT. Enzymeimmunoassays showed an increased production of PGE2 in the IPC group. Treatment of hearts with indomethacin blocked the protective effect of IPC on the vasodilatation produced by 5-HT and decreased the production of PGE2. A 5-min perfusion with 3 nM PGE2 started 15 min before the partial ischaemia, protected the endothelium. This was blocked by 1 microM chelerythrine, but not by 0.3 microM glibenclamide.
These results suggest that IPC affords protection to endothelial function in coronary arteries of the rat partially via the release of PGE2. Under our experimental conditions, the protective effect of PGE2 is mediated by PKC.
评估缺血预处理（IPC）对大鼠冠状动脉内皮功能的保护作用是否涉及前列腺素。
将在恒流条件下灌注的离体大鼠心脏暴露于30分钟的部分缺血（流速1毫升/分钟），随后再灌注20分钟，之后用0.1微摩尔/升的U-46619使冠状动脉预收缩，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/升）的反应与对内皮非依赖性血管舒张剂硝普钠（SNP，3微摩尔/升）的反应进行比较。在IPC或相应的假手术期前15分钟开始用10微摩尔/升的吲哚美辛灌注，阻断前列腺素的产生，并在20分钟再灌注期前停止。
与假手术组心脏相比，未经处理的心脏中，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引起的血管舒张未受影响。IPC（在30分钟部分缺血前进行5分钟零流量缺血，随后再灌注10分钟）保留了5-HT产生的血管舒张作用。酶免疫分析显示IPC组中PGE2的产生增加。用吲哚美辛处理心脏可阻断IPC对5-HT产生的血管舒张的保护作用，并降低PGE2的产生。在部分缺血前15分钟开始用3纳摩尔/升的PGE2灌注5分钟，可保护内皮。这被1微摩尔/升的白屈菜红碱阻断，但未被0.3微摩尔/升的格列本脲阻断。
这些结果表明，IPC部分通过释放PGE2对大鼠冠状动脉内皮功能提供保护。在我们的实验条件下，PGE2的保护作用由蛋白激酶C介导。
