Role of Bradykinin in Protection of Ischemic Preconditioning in Rabbit Hearts

摘要: Bradykinin receptor activation has been proposed to be involved in ischemic preconditioning. In the present study, we further investigated role of this agent preconditioning both isolated and situ rabbit hearts. All hearts were subjected 30 minutes regional ischemia followed by reperfusion for 2 hours (in vitro hearts) 3 hearts). Infarct size was measured tetrazolium staining expressed as a percentage risk zone. Preconditioning with 5 10 significantly reduced infarct 10.2 +/- 2.2% region (P < .0005 versus control 36.7 2.6%). Pretreatment HOE 140 (26 micrograms/kg), bradykinin B2 blocker, did not alter nonpreconditioned (40.6 5.3% infarction) but abolished protection from (34.1 1.6% infarction). However, when administered during initial reflow period following ischemia, no longer (15.6 3.9% infarction 13.3 3.8% without 140, P = NS). infusion mimicked preconditioning, affected pretreatment nitric oxide synthase inhibitor N omega-nitro-L-arginine methyl ester or prostaglandin synthesis indomethacin could completely protein kinase C (PKC) inhibitors polymyxin B staurosporine well 140. block That failure apparently due absence blood-borne kininogens rather than autonomic nerves. When stimulus model amplified four cycles 5-minute ischemia/10-minute reperfusion, (infarct 10.7 3.5% 6.4 2.0% We propose that receptors protect coupling PKC do adenosine receptors, blockade either will diminish total below threshold prevent protection. A more intense can overcome blockade, however, simply enhancing amount possibly other agonists released.