Bugge E, Ytrehus K
Department of Medical Physiology, University of Tromsø, Norway.
J Mol Cell Cardiol. 1996 Dec;28(12):2333-41. doi: 10.1006/jmcc.1996.0226.
The aim of the study was to test if pre-ischemic treatment with bradykinin can protect against infarction in an isolated rat heart model of regional ischemia and reperfusion, and if any such protection is dependent upon activation of protein kinase C (PKC) or mediated through the nitric oxide (NO) pathway. We also investigated if bradykinin B2 receptor activation, alone or in combination with activation of adenosine receptors and alpha-adrenoceptors, are involved in the infarct size reducing effect of ischemic preconditioning. Buffer-perfused rat hearts were subjected to 30 min regional ischemia and 120 min reperfusion. Risk zone was determined by fluorescent particles and infarct size by tetrazolium staining. Treatment with bradykinin (0.5 mumol/l) prior to ischemia significantly reduced infarct size in percentage of risk zone compared to control experiments (infarct size: 9.6 +/- 1.3% v 41.8 +/- 3.6%, P < 0.001). An inhibitor of NO synthesis, NOARG (100 mumol/l), did not interfere with the bradykinin induced protection (infarct size: 13.3 +/- 2.0%), while chelerythrine (2 mumol/l), an inhibitor of protein kinase C, reversed the effect of bradykinin (infarct size: 30.0 +/- 2.8%). NOARG did not influence infarct size in the control group (infarct size: 40.1 +/- 3.2%). Ischemic preconditioning with three cycles of 5 min global ischemia + 5 min reperfusion offered protection similar to bradykinin (infarct size: 8.4 +/- 2.0%). The bradykinin antagonist HOE 140 (1 mumol/l) reversed the effect of bradykinin (infarct size: 42.5 +/- 3.1%), but did not interfere with ischemic preconditioning (infarct size: 7.7 +/- 1.6%). Similarily, combined blockade of alpha-adrenergic, adenosine and bradykinin B2 receptors with p-benzamine (10 mumol/l). SPT (100 mumol/l) and HOE 140 did not interfere with ischemic preconditioning (infarct size: 7.8 +/- 1.1%). Thus, bradykinin can protect against infarction via protein kinase C, but independently of NO. A role for bradykinin in mediating ischemic preconditioning against infarction could not be demonstrated.
本研究的目的是测试在局部缺血和再灌注的离体大鼠心脏模型中，缓激肽的缺血预处理是否能预防梗死，以及任何此类保护作用是否依赖于蛋白激酶C（PKC）的激活或通过一氧化氮（NO）途径介导。我们还研究了缓激肽B2受体激活单独或与腺苷受体和α-肾上腺素能受体激活联合是否参与缺血预处理的梗死面积减小效应。用缓冲液灌注的大鼠心脏经历30分钟局部缺血和120分钟再灌注。通过荧光颗粒确定危险区，通过四氮唑染色确定梗死面积。与对照实验相比，缺血前用缓激肽（0.5μmol/L）处理显著降低了梗死面积占危险区的百分比（梗死面积：9.6±1.3%对41.8±3.6%，P<0.001）。NO合成抑制剂NOARG（100μmol/L）不干扰缓激肽诱导的保护作用（梗死面积：13.3±2.0%），而蛋白激酶C抑制剂白屈菜红碱（2μmol/L）逆转了缓激肽的作用（梗死面积：30.0±2.8%）。NOARG不影响对照组的梗死面积（梗死面积：40.1±3.2%）。用三个5分钟全心缺血+5分钟再灌注周期进行缺血预处理提供了与缓激肽相似的保护作用（梗死面积：8.4±2.0%）。缓激肽拮抗剂HOE 140（1μmol/L）逆转了缓激肽的作用（梗死面积：42.5±3.1%），但不干扰缺血预处理（梗死面积：7.7±1.6%）。同样，用对苄胺（10μmol/L）、SPT（100μmol/L）和HOE 140联合阻断α-肾上腺素能、腺苷和缓激肽B2受体不干扰缺血预处理（梗死面积：7.8±1.1%）。因此，缓激肽可通过蛋白激酶C预防梗死，但不依赖于NO。未证实缓激肽在介导缺血预处理抗梗死中的作用。
