Role of bradykinin in the vasodilator effects of losartan and enalapril inpatients with heart failure

Background-ACE inhibitors have been shown to potentiate the effects of exog enous bradykinin by inhibition of its breakdown. Despite this, there is lit tle evidence that inhibition of endogenous bradykinin breakdown actually co ntributes to the effects of ACE inhibitors, or indeed, other inhibitors of the renin-angiotensin system, such as angiotensin II type I receptor (AT,) antagonists, and no evidence at all that it does so in patients with heart failure. Methods and Results-Twelve patients with heart failure (11 male, 1 female, ages 59 to 81 years) were randomized to double-blind crossover treatment wi th enalapril 10 mg BID followed by losartan 25 mg BID, or the reverse, each for 5 weeks. At the end of each treatment period, forearm blood flow was m easured by venous occlusion plethysmography during an intrabrachial infusio n of bradykinin before and after an intrabrachial infusion of Hoe-140 (a po tent, selective, and long-acting bradykinin antagonist). Bradykinin caused profound vasodilatation after enalapril (peak, 357+/-67%) and less after lo sartan (peak, 230+/-46%). Despite this, Hoe-140 had no discernible effects after enalapril or losartan. Similarly, this was despite the finding that H oe-140 significantly reduced vasodilatation to bradykinin after enalapril ( peak, 192+/-35%) and losartan (peak, 66+/-13%). Conclusions-Inhibition of endogenous bradykinin breakdown does not appear t o contribute to the effects of ACE inhibition or AT(1) antagonism in the fo rearm of patients with heart failure at rest, despite the very obvious effe cts of ACE inhibition compared with AT(1) antagonism on exogenous bradykini n.