Effect of lipopolysaccharide, cytokines, and catecholamines on brain natriuretic peptide release from human myocardium.

Abstract

During sepsis and septic shock, elevated plasma concentrations of brain natriuretic peptide (BNP) have been reported but may be related to several underlying mechanisms. The aim of the present experimental study was to investigate the effect of lipopolysaccharide (LPS), tumor necrosis factor α (TNF-α), interleukin 1β (IL-1β), interleukin 6 (IL-6), dobutamine (Dobu), epinephrine (Epi), and norepinephrine (Nor) on BNP synthesis by atrial human myocardium in vitro. After the approval of local ethics committee, right atrial appendages were obtained during cannulation for cardiac surgery and pinned in a isolated organ bath containing 15 ml of Tyrode's modified solution. Preparations were oxygenated, maintained at 36 ± 0.5°C and stimulated at a frequency of 1 Hz. A 60-min equilibration period was followed by 180-min exposure to 1 μM endothelin 1 (ET-1; n = 9), 20,000 pg/ml TNF-α (n = 10), 1000 pg/ml IL-1β (n = 10), 5000 pg/ml IL-6 (n = 10), 10,000 pg/ml LPS (n = 10), 100 μM Epi (n = 9), 100 μM Nor (n = 10), and 100 μM Dobu (n = 8). No product was added in Control group (n = 10). Two BNP dosages were performed: the first after 60 min of stabilization and the second after 180 min of stimulation. Absolute and relative changes in BNP concentration were compared between groups. Exposure to ET-1 significantly increased BNP release as compared with Control group. Dobu, Epi, Nor, and LPS significantly increased BNP concentration but not TNF-α, IL-1β, or IL-6. In vitro, LPS, Dobu, Epi, and Nor induced BNP synthesis by human atrial myocardium.