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

被引:34
作者
Davie, AP [1 ]
Dargie, HJ [1 ]
McMurray, JJV [1 ]
机构
[1] Univ Glasgow, MRC, Clin Res Initiat Heart Failure, Glasgow G12 8QQ, Lanark, Scotland
关键词
bradykinin; angiotensin; vasodilation; heart failure;
D O I
10.1161/01.CIR.100.3.268
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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 (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 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 AT(1) antagonism in the forearm of patients with heart failure at rest, despite the very obvious effects of ACE inhibition compared with AT(1) antagonism on exogenous bradykinin.
引用
收藏
页码:268 / 273
页数:6
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