Induction of
congestive heart failure by high-frequency pacing has been reported to increase plasma levels of immunoreactive
kinins in dogs. In the present study, we evaluated plasma
bradykinin levels in human
heart failure. Utilizing a recently developed method, we specifically measured plasma levels of bradykinin-(1-9) nonapeptide in 21 patients with chronic
congestive heart failure [New York Heart Association (NYHA) stages III and IV). At the same time, we measured plasma
atrial natriuretic peptide levels and plasma
renin activity, and, as a marker of
inflammation, plasma levels of tumour
necrosis factor. In addition, 18 healthy subjects matched for gender and age served as normal controls. Plasma
bradykinin concentrations were not higher in patients with chronic
congestive heart failure (median 2.1 fmol/ml) than in healthy subjects (2.6 fmol/ml). In contrast, plasma
atrial natriuretic peptide levels were clearly higher (patients, 63 fmol/ml; controls, 24 fmol/ml; P<0.0001), despite
diuretic treatment and in the presence of high plasma
renin activity (patients, 13.0 ng x h(-1) x ml(-1); controls, 0.3 ng x h(-1) x ml(-1); P<0.0001). Tumour
necrosis factor was elevated in
heart failure patients in NYHA class IV only (27 pg/ml, compared with 21 pg/ml in controls; P=0.013).
Bradykinin,
atrial natriuretic peptide and plasma
renin activity levels were not correlated with the severity of the disease, as assessed by NYHA classification. These results indicate that a rather selective
cytokine activation, without concomitant stimulation of the kallikrein-kinin system, occurs in human chronic
congestive heart failure.