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 μg/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), pulmonary arterial wedge pressure (−1.4 mm Hg), and mean pulmonary arterial pressure (−1.3 mm Hg) were greater compared with losartan (P