Impaired bradykinin response to ischaemia and exercise in patients with mild congestive heart failure during angiotensin-converting enzyme treatment : relationships with endothelial function, coagulation and inflammation

Background: inflammation and endothelial dysfunction play important roles in the pathophysiology of congestive heart failure (CHF), and the vasoactive peptide bradykinin, generated during inflammation, may act as a defense mechanism. Plasma bradykinin levels are increased in experimental heart failure but low in patients with advanced chronic CHF despite treatment with angiotensin-converting enzyme (ACE) inhibitors. To date it is not known how bradykinin behaves in less severe phases of CHF controlled by long-term ACE inhibitor treatment Methods: we studied 10 male patients with clinically stable chronic CHF (NYHA class II) on long-term ACE inhibitor treatment and 10 normal sex- and age-matched control subjects. We evaluated with an HPLC/RIA method plasma levels of bradykinin in relation to an array of parameters of endothelial function, coagulation and inflammation before and after stimuli of forearm arterial occlusion and physical exercise Results: CHF patients had higher levels of bradykinin (P=0.008), activated factorXII (P=0.049), interleukin-6 (P=0.050) and tumor necrosis factor receptor II (sTNFRII) (P=0.026) than controls. Arterial occlusion and exercise significantly increased bradykinin and von Willebrand factor levels in controls but not in CHF patients. The increase in brachial artery diameter after arterial occlusion was less in CHF patients (P=0.036) and inversely related to baseline plasma levels of bradykinin (r=-0.855, P=0.002) and sTNFRII (r=-0.780, P=0.008) Conclusions: NYHA class II CHF patients during long-term treatment with ACE inhibitors have increased bradykinin levels and signs of inflammation. They are unable to respond adequately to stimuli of ischemia and physical exercise which both require vasodilation.