TY - JOUR
T1 - Endotoxin and tumor necrosis factor α exert a similar proinflammatory effect in neonatal rat cardiomyocytes, but have different cardiodepressant profiles
AU - Müller-Werdan, Ursula
AU - Schumann, Heike
AU - Loppnow, Harald
AU - Fuchs, Ralph
AU - Darmer, Dorothea
AU - Stadler, Josef
AU - Holtz, Jürgen
AU - Werdan, Karl
N1 - Funding Information:
This study was supported by the Deutsche For-schungsgemeinschaft (Mu 1010/1-4,-5, Sta 311/
Funding Information:
2-1) and by Bundesministerium für Bildung und Forschung (BMBF, grant no. 01ZZ9512).
PY - 1998/5
Y1 - 1998/5
N2 - Bolus application of endotoxin to healthy volunteers results in reversible hemodynamic alterations, such as observed in septic cardiomyopathy. Currently, endotoxin-induced cardiodepression is mainly attributed to the endotoxin-induced release of proinflammatory cytokines into the circulation, particularly of tumor necrosis factor α and interleukin-1, the serum levels of these cytokines being enhanced in sepsis and septic shock, and also in various heart diseases. In this study, we report a proinflammatory effect of endotoxin (1-10 μg/ml, 24-h incubation period) on neonatal rat cardiomyocytes in serum-free culture, evidenced by induction of inducible nitric oxide synthase, enhanced release of nitrite (protein synthesis-dependent) and interleukin-6 into the supernatant, as well as an increase in cell-associated interleukin-1 and a specific cardiodepressant profile: endotoxin disrupts β-adrenoceptor-mediated increase in pulsation amplitude, but α-adrenoceptor-induced increase in pulsation amplitude and arrhythmias are not suppressed. In the presence of dexamethasone (0.1 μM), the endotoxin-mediated blockade of β-adrenergic responsiveness, as well as induction of inducible nitric oxide synthase, enhanced nitrite release and interleukin-1/-6-production are inhibited. In contrast, tumor necrosis factor α at a low concentration (10 U/ml) depresses α- and β-adrenergic responsiveness in the presence of dexamethasone in a nitric oxide-independent manner. These data suggest a stimulatory effect of endotoxin on the cardiomyocyte and a specific proinflammatory and nitric oxide-dependent cardiodepressant profile of endotoxin.
AB - Bolus application of endotoxin to healthy volunteers results in reversible hemodynamic alterations, such as observed in septic cardiomyopathy. Currently, endotoxin-induced cardiodepression is mainly attributed to the endotoxin-induced release of proinflammatory cytokines into the circulation, particularly of tumor necrosis factor α and interleukin-1, the serum levels of these cytokines being enhanced in sepsis and septic shock, and also in various heart diseases. In this study, we report a proinflammatory effect of endotoxin (1-10 μg/ml, 24-h incubation period) on neonatal rat cardiomyocytes in serum-free culture, evidenced by induction of inducible nitric oxide synthase, enhanced release of nitrite (protein synthesis-dependent) and interleukin-6 into the supernatant, as well as an increase in cell-associated interleukin-1 and a specific cardiodepressant profile: endotoxin disrupts β-adrenoceptor-mediated increase in pulsation amplitude, but α-adrenoceptor-induced increase in pulsation amplitude and arrhythmias are not suppressed. In the presence of dexamethasone (0.1 μM), the endotoxin-mediated blockade of β-adrenergic responsiveness, as well as induction of inducible nitric oxide synthase, enhanced nitrite release and interleukin-1/-6-production are inhibited. In contrast, tumor necrosis factor α at a low concentration (10 U/ml) depresses α- and β-adrenergic responsiveness in the presence of dexamethasone in a nitric oxide-independent manner. These data suggest a stimulatory effect of endotoxin on the cardiomyocyte and a specific proinflammatory and nitric oxide-dependent cardiodepressant profile of endotoxin.
KW - Cardiodepression
KW - Cardiomyocytes
KW - Catecholamines
KW - Contractility
KW - Cytokine-induction
KW - Endotoxin
KW - Inducible nitric oxide synthase
KW - Interleukin
KW - Tumor necrosis factor α
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U2 - 10.1006/jmcc.1998.0667
DO - 10.1006/jmcc.1998.0667
M3 - Article
C2 - 9618243
AN - SCOPUS:16744363828
SN - 0022-2828
VL - 30
SP - 1027
EP - 1036
JO - Journal of Molecular and Cellular Cardiology
JF - Journal of Molecular and Cellular Cardiology
IS - 5
ER -