Antagonizing bradykinin (BK) obliterates the cardioprotective effects of bradykinin and angiotensin-converting enzyme (ACE) Inhibitors in ischemic hearts

Bradykinin (BK) (1 × 10 ^?12?1 × 10^?8 mol/l) and the ACE inhibitor ramiprilat (2.58 × 10 ^?9?2.58 × 10^?5 mol/l) markedly reduced the incidence and duration of reperfusion arrhythmias in the isolated ischemic rat heart. Pretreatment with ramipril (1 mg/kg p.o.), enalapril (10 mg/kg p.o.), but not captopril (50 mg/kg p.o.) had similar effects. Active compounds also improved cardiodynamics and reduced lactate dehydrogenase (LDH) and creatine kinase (CK) activities, as lactate formation in coronary venous effluent. Cardiac tissue levels of glycogen, adenosine triphosphate (ATP), and creatine phosphate (CP) were preserved. The BK antagonist D-Arg-Hyp², Thi^5,8, D-Phe⁷]BK abolished the beneficial effects of BK, ramipril, and ramiprilat in a competitive way. Increased concentrations of BK or ramiprilat were able to reverse the antagonism. In anesthetized dogs an infusion of BK, at the dose of 1 ng/kg/min during coronary occlusion and reperfusion was devoid of cardiovascular effects but reduced mortality and the decrease of LDH activity and lactate concentration in coronary sinus blood and preserved tissue levels of glycogen and energy-rich phosphates in the ischemic myocardium.