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.
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Received: 11 October 1996 / Accepted: 27 November 1996
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Abadie, C., Foucart, S., Pagé, P. et al. Interleukin-1β and tumor necrosis factor-α inhibit the release of [3H]-Noradrenaline from isolated human atrial appendages. Naunyn-Schmiedeberg's Arch Pharmacol 355, 384–389 (1997). https://doi.org/10.1007/PL00004958
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DOI: https://doi.org/10.1007/PL00004958