ROLE OF BRADYKININ IN CARDIAC FUNCTIONAL PROTECTION AFTER GLOBAL ISCHEMIA-REPERFUSION IN RAT-HEART

We have reported that cardiac preconditioning against ischemia-reperfu sion (IR) can be induced by transient ischemia (TI) and alpha(1)-adren oreceptor stimulation, both mediated by protein kinase C (PKC) (Mitche ll, M., X. Meng, C. Parker, E. Brew, A. Harken, and A. Banerjee. Circ. Res. 76: 73-81, 1995.). Our study objective was to explore the mechan ism of endogenous preconditioning and address the role of PKC activati on in bradykinin-mediated cardiac functional protection. Isolated rat heart was used to assess the effects of exogenous bradykinin, TI, sele ctive B-2-receptor blocker, and PKC antagonism on cardiac functional r ecovery after a global IR injury. Final recovery of developed pressure was improved in hearts treated with bradykinin and TI compared with c ontrols. Bradykinin- and TI-mediated preconditioning was eliminated wi th coinfusion of the B-2-receptor antagonist. Further evaluation of br adykinin-mediated preconditioning revealed that PKC blockade also elim inated functional protection. Immunofluorescent stains of bradykinin-t reated hearts demonstrated translocation and activation of specific PK C isoforms in the preconditioned heart. We conclude that TI-mediated p reconditioning involves intrinsic cardiac bradykinin receptor stimulat ion. Bradykinin, through the B-2 receptor, initiates a series of intra cellular events culminating in the activation of PKC.