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Naunyn-Schmiedeberg's Archives of Pharmacology

, Volume 355, Issue 3, pp 384–389 | Cite as

Interleukin-1β and tumor necrosis factor-α inhibit the release of [3H]-Noradrenaline from isolated human atrial appendages

  • Claire Abadie
  • S. Foucart
  • Pierre Pagé
  • Réginald Nadeau
ORIGINAL ARTICLE

Abstract

In the present study, we have investigated the ability of human recombinant interleukin-1β (hIL-1β) and human recombinant tumor necrosis factor-α (hTNF-α) to modulate the stimulation-induced (S-I) outflow of [3H]-noradrenaline ([3H]-NA) from isolated superfused human atria. Pieces of human right atrial appendages were excised during routine cardiac surgery. Tissues were incubated with [3H]-NA (0.2 μmol/l) for 30 min at 37°C, then inserted in a Brandel suprafusion system where the radioactivity was washed for 75 min with a Krebs-Henseleit solution at a rate of 0.4 ml/min. Thereafter, the effluent was collected for the remainder of the protocol during which two trains of electrical stimulation (50 mA intensity, 5 Hz frequency, 60 s duration, 2 ms pulses) were delivered at 10 min and 45 min (short protocol) or 85 min (long protocol). The effect of drugs on the S-I outflow of [3H]-NA was determined by adding drugs 20 min (short protocol) or 60 min (long protocol) before the second stimulation. Experiments were carried out in the continuous presence of desipramine (1 μmol/l) to prevent neuronal NA reuptake. The results showed that in human atrium, hIL-1β (3 ng/ml) and hTNF-α (0.5 ng/ml) significantly inhibited the S-I release of [3H]-NA. The inhibitory effect of hIL-1β was blocked by human recombinant IL-1 receptor antagonist (50 ng/ml), and by the cyclooxygenase inhibitor, diclofenac (1 μmol/l), suggesting that hIL-1β inhibited NA release through the formation of prostaglandins. The ability of hIL-1β and hTNF-α to inhibit NA release suggest that mediators of the immune system produced locally may modulate the activity of the sympathetic nervous system in human atrial appendages.

Key words Human atrial appendage Noradrenaline release Presynaptic modulation Cytokines Interleukin-1β Tumor necrosis factor-α 

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Copyright information

© Springer-Verlag Berlin Heidelberg 1997

Authors and Affiliations

  • Claire Abadie
    • 2
  • S. Foucart
    • 1
  • Pierre Pagé
    • 3
  • Réginald Nadeau
    • 4
  1. 1.Centre de Recherche, Hôpital du Sacré-Coeur de Montréal, 5400 boul. Gouin ouest, Montréal, Québec, Canada, H4J 1C5CA
  2. 2.Research Centre, Hôpital du Sacré-Coeur de Montréal, Groupe de Recherche sur le Système Nerveux Autonome, Departments of Physiology, Université de Montréal, Montréal, Québec, CanadaCA
  3. 3.Research Centre, Hôpital du Sacré-Coeur de Montréal, Groupe de Recherche sur le Système Nerveux Autonome, Departments of Surgery, Université de Montréal, Montréal, Québec, CanadaCA
  4. 4.Research Centre, Hôpital du Sacré-Coeur de Montréal, Groupe de Recherche sur le Système Nerveux Autonome, Departments of Medicine, Université de Montréal, Montréal, Québec, CanadaCA

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