Endotoxin and tumor necrosis factor α exert a similar proinflammatory effect in neonatal rat cardiomyocytes, but have different cardiodepressant profiles

Ursula Müller-Werdan, Heike Schumann, Harald Loppnow, Ralph Fuchs, Dorothea Darmer, Josef Stadler, Jürgen Holtz, Karl Werdan

Research output: Contribution to journalArticlepeer-review

64 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1027-1036
Number of pages10
JournalJournal of Molecular and Cellular Cardiology
Volume30
Issue number5
DOIs
StatePublished - May 1998
Externally publishedYes

Keywords

  • Cardiodepression
  • Cardiomyocytes
  • Catecholamines
  • Contractility
  • Cytokine-induction
  • Endotoxin
  • Inducible nitric oxide synthase
  • Interleukin
  • Tumor necrosis factor α

ASJC Scopus subject areas

  • Molecular Biology
  • Cardiology and Cardiovascular Medicine

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