Bradykinin protects against infarction but does not mediate ischemic preconditioning in the isolated rat heart.

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.