(Circulation. 1999;100:268-273.)
© 1999 American Heart Association, Inc.
Clinical Investigation and Reports |
Role of Bradykinin in the Vasodilator Effects of Losartan and Enalapril in Patients With Heart Failure
From the Medical Research Council Clinical Research Initiative in Heart Failure, University of Glasgow, Glasgow, UK.
Correspondence to Dr Andrew P. Davie, MRC Clinical Research Initiative in Heart Failure, University of Glasgow, Glasgow G12 8QQ, UK. E-mail a.davie{at}bio.gla.ac.uk
Background—ACE inhibitors have been shown to potentiate the effects of exogenous bradykinin by inhibition of its breakdown. Despite this, there is little evidence that inhibition of endogenous bradykinin breakdown actually contributes to the effects of ACE inhibitors, or indeed, other inhibitors of the renin-angiotensin system, such as angiotensin II type I receptor (AT1) 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 with 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 measured by venous occlusion plethysmography during an intrabrachial infusion of bradykinin before and after an intrabrachial infusion of Hoe-140 (a potent, selective, and long-acting bradykinin antagonist). Bradykinin caused profound vasodilatation after enalapril (peak, 357±67%) and less after losartan (peak, 230±46%). Despite this, Hoe-140 had no discernible effects after enalapril or losartan. Similarly, this was despite the finding that Hoe-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 to contribute to the effects of ACE inhibition or AT1 antagonism in the forearm of patients with heart failure at rest, despite the very obvious effects of ACE inhibition compared with AT1 antagonism on exogenous bradykinin.
Key Words: bradykinin • angiotensin • vasodilation • heart failure
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