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Dual effect of nicotine on cardiac noradrenaline release during metabolic blockade

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Summary

Nicotine-induced noradrenaline was investigated in perfused guinea pig hearts subjected to metabolic blockade that was caused either by anoxia or by cyanide intoxication. Noradrenaline, neuropeptide Y, and dihydroxyphenylethyleneglycol (DOPEG) were determined in the coronary venous overflow. Neuropeptide Y is a sympathetic cotransmitter of nordrenaline, and concomitant release of both transmitters indicates an exocytotic, calcium-dependent release mechanism, whereas neuropeptide Y overflow does not occur during nonexocytotic noradrenaline release. Nonexocytotic, calcium-independent noradrenaline release, however, is associated with an increase of DOPEG overflow, which is the main intraneuronal metabolite of noradrenaline formed by monoamine oxidase if oxygen is present.

Anoxia per se caused a nonexocytotic release of noradrenaline starting after 10 min of anoxia and reaching peak levels at 30 min. During anoxia, nicotine (3 and 10 μmol/l) accelerated and enhanced noradrenaline overflow, i.e., the period between the onset of anoxia and the begin of noradrenaline release was shortened and peak levels were increased. Nicotine-induced noradrenaline release was accompanied by neuropeptide Y overflow. The action of nicotine was further evaluated during energy depletion caused by cyanide. As anoxia did, cyanide administration alone resulted in noradrenaline release. In accordance with a nonexocytotic mechanism and due to the presence of oxygen, this release of noradrenaline was accompanied by an increase of DOPEG. When added 10 min after the onset of energy depletion, nicotine (10 μmol/l) caused a brief but marked enhancement of exocytotic noradrenaline release, since this release was calcium-dependent and was accompanied by a significnat rise of neuropeptide Y overflow. In absence of extracellular calcium to avoid exocytosis, concomitant administration of nicotine (3–100 μmol/l) and cyanide caused a concentration- dependent acceleration of both the overflow of noradrenaline and DOPEG, whereas overflow of neuropeptide Y was not increased, thus indicating a nonexocytotic release mechanism.

In conclusion, the application of nicotine during myocardial energy depletion increases overflow of noradrenaline by both calcium-dependent exocytotic release and calcium-independent nonexocytotic release mechanisms.

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Author notes

  1. G. Richardt

    Present address: 1. Medizinische Klinik, Technische Universität München, Klinikum rechts der Isar, Ismaninger Str. 22, 81675, München, Germany

Authors and Affiliations

  1. 1. Medizinische Klinik, Technische Universität München, Klinikum rechts der Isar, Ismaninger Str. 22, 81675, München, Germany

    T. Brenn, M. Seyfarth & A. Schömig

  2. Innere Medizin III, Universität Heidelberg, Heidelberg, Germany

    M. Haass

  3. Pharmakologie, Universität Heidelberg, Heidelberg, Germany

    E. Schömig

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  1. G. Richardt
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This work was supported by a grant from the “Forschungsrat Rauchen und Gesundheit”.

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Richardt, G., Brenn, T., Seyfarth, M. et al. Dual effect of nicotine on cardiac noradrenaline release during metabolic blockade. Basic Res Cardiol 89, 524–534 (1994). https://doi.org/10.1007/BF00794952

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  • DOI: https://doi.org/10.1007/BF00794952

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