Bradykinin contributes to the systemic hemodynamic effects of chronic angiotensin-converting enzyme inhibition in patients with heart failure

Background - Bradykinin is an endogenous vasodilator that may contribute to the systemic effects of angiotensin-converting enzyme (ACE) inhibitor therapy. Using B9340, a bradykinin receptor antagonist, we determined the contribution of bradykinin to the systemic hemodynamic effects of long-term ACE inhibition in patients with chronic heart failure. Methods and Results - Fourteen patients with heart failure received enalapril (10 mg twice daily) or losartan ( 50 mg twice daily) in a randomized double-blind crossover trial. After 6 weeks treatment, patients underwent right heart catheterization and were randomized to an intravenous infusion of B9340 (2 to 20 mug/kg per minute) or saline placebo. After B9340 infusion in patients treated with enalapril, mean arterial pressure (+5.2 mm Hg), systemic vascular resistance (+315 dynes.s/cm(5)), pulmonary arterial wedge pressure (-1.4 mm Hg), and mean pulmonary arterial pressure (-1.3 mm Hg) were greater compared with losartan (P < 0.005, P = 0.07, P < 0.0001, and P < 0.05 respectively) or placebo infusion (P ≤ 0.005 for all). There was a reduction in cardiac output after B9340 with enalapril compared with placebo (P < 0.001) but not losartan. Conclusions - Bradykinin contributes to the systemic hemodynamic effects of long-term ACE inhibition in patients with heart failure. This mechanism may explain the apparent clinical differences between ACE inhibitors and angiotensin receptor blockers in the treatment of heart failure.