Plasma bradykinin levels in human chronic congestive heart failure

Induction of congestive heart failure by high-frequency pacing has been rep orted to increase plasma levels of immunoreactive kinins in dogs. In the pr esent study, we evaluated plasma bradykinin levels in human heart failure. Utilizing a recently developed method, we specifically measured plasma leve ls of bradykinin-(1-9) nonapeptide in 21 patients with chronic congestive h eart 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 n ecrosis factor. In addition, 18 healthy subjects matched for gender and age served as normal controls. Plasma bradykinin concentrations were not highe r in patients with chronic congestive heart failure (median 2.1 fmol/ml) th an in healthy subjects (2.6 fmol/ml). In contrast, plasma atrial natriureti c peptide levels were clearly higher (patients, 63 fmol/ml; controls, 24 fm ol/ml; P < 0.0001), despite diuretic treatment and in the presence of high plasma renin activity (patients, 13.0 ng.h(-1).ml(-1); controls, 0.3 ng.h(- 1).ml(-1); P < 0.0001). Tumour necrosis factor was elevated in heart failur e patients in NYHA class IV only (27 pg/ml, compared with 21 pg/ml in contr ols; P = 0.013). Bradykinin, atrial natriuretic peptide and plasma renin ac tivity levels were not correlated with the severity of the disease, as asse ssed by NYHA classification. These results indicate that a rather selective cytokine activation, without concomitant stimulation of the kallikrein-kin in system, occurs in human chronic congestive heart failure.