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.
Inflammation and endothelial dysfunction play important roles in the pathophysiology of congestive heart failure (CHF), and the peptide bradykinin, generated during inflammation, may act as a defence mechanism by inducing vasodilation. 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. It is not currently known how bradykinin behaves in less severe phases of CHF controlled by long-term ACE inhibitor treatment. We studied 10 male patients with clinically stable chronic CHF [New York Heart Association (NYHA) class II] on long-term ACE inhibitor treatment and 10 normal sex- and age-matched control subjects. High performance liquid chromatography/radioimmunoassay methods were used to evaluate 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. CHF patients had higher levels of bradykinin (P = 0.008), activated factor XII (P = 0.049), interleukin-6 (P = 0.050) and tumour 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). 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 ischaemia and physical exercise which both require vasodilation.
Department of Internal Medicine, University of Milan, Milan, Italy. massimo.cugno@unimi.it
Massimo
M
Cugno
Piergiuseppe
P
Agostoni
Daniela
D
Mari
Pier Luigi
PL
Meroni
Luisa
L
Gregorini
Maurizio
M
Bussotti
Gian Battista
GB
Anguissola
Francesco
F
Donatelli
Jürg
J
Nussberger
D000328:Adult; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D001779:Blood Coagulation Factors / Q000032:analysis; D001916:Brachial Artery / Q000000981:diagnostic imaging; D001920:Bradykinin / Q000097:blood*; D016022:Case-Control Studies; D004730:Endothelium, Vascular / Q000503:physiopathology; D015444:Exercise; D015956:Factor XIIa / Q000032:analysis; D006333:Heart Failure / Q000097:blood* / Q000188:drug therapy* / Q000503:physiopathology; D006801:Humans; D015850:Interleukin-6 / Q000097:blood; D007511:Ischemia / Q000503:physiopathology; D017706:Lisinopril / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D047889:Receptors, Tumor Necrosis Factor, Type II / Q000097:blood; D010959:Tissue Plasminogen Activator / Q000032:analysis; D014463:Ultrasonography; D014664:Vasodilation; D014841:von Willebrand Factor / Q000032:analysis
D000806:Angiotensin-Converting Enzyme Inhibitors; D015415:Biomarkers; D001779:Blood Coagulation Factors; D015850:Interleukin-6; D047889:Receptors, Tumor Necrosis Factor, Type II; D014841:von Willebrand Factor; D017706:Lisinopril; D015956:Factor XIIa; D010959:Tissue Plasminogen Activator; D001920:Bradykinin