Starkopf J, Bugge E, Ytrehus K
Department of Biochemistry, Faculty of Medicine, University of Tartu, Estonia.
Cardiovasc Res. 1997 Jan;33(1):63-70. doi: 10.1016/s0008-6363(96)00195-2.
Substantial release of bradykinin has been demonstrated to occur during short periods of myocardial ischaemia in various species. The aim of the present study was to investigate the protective effect of bradykinin in ischaemia and whether bradykinin could be involved in ischaemic preconditioning in the rat heart.
Isolated, buffer-perfused hearts were subjected to 30 min of global ischaemia, followed by 30 min of reperfusion. Postischaemic functional recovery was recorded in the following groups: (1) control; (2) treatment with 0.1 microM bradykinin for 10 min before ischaemia (BK); (3) bradykinin treatment combined with pretreatment with the specific bradykinin B2-receptor antagonist, HOE 140; (4) ischaemic preconditioning by 5 min ischaemia +5 min reperfusion prior to sustained ischaemia (i.p.); and (5) ischaemic preconditioning combined with HOE 140 administration.
Postischaemic myocardial function was significantly improved in both BK and i.p. groups (developed pressure 66.9 +/- 6.8 and 67.6 +/- 7.1 mmHg, respectively, vs. 43.1 +/- 5.9 mmHg in controls, P < 0.05). Pretreatment with 1 microM HOE 140 completely abolished the effect of bradykinin, while protection achieved by i.p. was unaltered by this drug. None of the protective interventions was associated with any significant improvement in myocardial adenosine triphosphate, creatine phosphate, glycogen, lactate or glucose tissue levels, detected either at the end of ischaemia or after 30 min of reperfusion.
Bradykinin, acting via B2-receptors, can protect against postischaemic contractile dysfunction to a similar extent as i.p.. An involvement of B2-receptors in the ischaemic preconditioning phenomenon could, however, not be demonstrated.
在多种物种的心肌缺血短时间内，已证实有大量缓激肽释放。本研究的目的是调查缓激肽在缺血中的保护作用，以及缓激肽是否参与大鼠心脏的缺血预处理。
将离体的、用缓冲液灌注的心脏进行30分钟全心缺血，随后再灌注30分钟。记录以下几组缺血后功能恢复情况：（1）对照组；（2）缺血前用0.1微摩尔缓激肽处理10分钟（BK组）；（3）缓激肽处理联合用特异性缓激肽B2受体拮抗剂HOE 140预处理；（4）在持续性缺血前进行5分钟缺血+5分钟再灌注的缺血预处理（i.p.组）；（5）缺血预处理联合HOE 140给药。
BK组和i.p.组缺血后心肌功能均显著改善（分别为舒张末压力66.9±6.8和67.6±7.1毫米汞柱，而对照组为43.1±5.9毫米汞柱，P<0.05）。用1微摩尔HOE 140预处理完全消除了缓激肽的作用，而i.p.组所实现的保护作用不受该药物影响。在缺血结束时或再灌注30分钟后检测，没有一种保护干预措施与心肌三磷酸腺苷、磷酸肌酸、糖原、乳酸或葡萄糖组织水平的任何显著改善相关。
缓激肽通过B2受体发挥作用，可在与缺血预处理相似的程度上预防缺血后收缩功能障碍。然而，未能证实B2受体参与缺血预处理现象。
