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 bradyk inin can protect against infarction in an isolated rat heart model of regional ischemia and reperfusion and if any such protection is depend ent upon activation of protein kinase C (PKC) or mediated through the nitric oxide (NO) pathway. Mie also investigated if bradykinin B-2 rec eptor activation, alone or in combination with activation of adenosine receptors and a-adrenoceptors, are involved in the infarct size reduc ing effect of ischemic preconditioning. Buffer-perfused rat hearts wer e subjected to 30 min regional ischemia and 120 min reperfusion. Risk zone was determined by fluorescent particles and infarct size by tetra zolium staining. Treatment with bradykinin (0.5 mu mol/l) prior to isc hemia significantly reduced infarct size in percentage of risk zone co mpared to control experiments (infarct size: 9.6 +/- 1.3% v 41.8 +/- 3 .6%, P<0.001). An inhibitor of NO synthesis, NOARG (100 mu mol/l). did not interfere with the bradykinin induced protection (infarct size: 1 3.3 +/- 2.0%), while chelerythrine (2 mu mol/l), an inhibitor of prote in kinase C, reversed the effect of bradykinin (infarct size: 30.0 +/- 2.8%). NOARG did not influence infarct size in the control group (inf arct size: 40.1 +/- 3.2%). Ischemic preconditioning with three cycles of 5 min global ischemia + 5 min reperfusion offered protection simila r to bradykinin (infarct size: 8.4 +/- 2.0%). The bradykinin antagonis t HOE 140 (1 mu mol/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 or-adre nergic, adenosine and bradykinin B-2 receptors with p-benzamine (10 mu mol/l), SPT (100 mu mol/l) and HOE 140 did not interfere with ischemi c preconditioning (infarct size: 7.8 +/- 1.1%). Thus, bradykinin can p rotect against infarction via protein kinase C, but independently of N O. A role for bradykinin in mediating ischemic preconditioning against infarction could not be demonstrated. (C) 1996 Academic Press Limited