Summary
In segments of the rat inferior vena cava preincubated with 3H-noradrenaline, it was examined whether presynaptic serotonin (5-HT) receptors exist on the postganglionic sympathetic nerves of the circulatory system; for this purpose the effects of 5-HT receptor agonists and antagonists on the electrically evoked 3H overflow were studied. Furthermore, vagotomized pithed rats (treated with atropine and captopril) were used to investigate the effects of these drugs on heart rate and on the tachycardia induced by electrical stimulation of the preganglionic sympathetic nerves (C7−T1) via the pithing rod; these experiments were carried out to provide evidence that the presynaptic 5-HT receptors are operative in vivo.
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1.
5-HT and 5-methoxytryptamine (5-OCH3-T) concentration-dependently inhibited the electrically evoked 3H overflow from the vena cava. The inhibitory effect was more pronounced at 0.66 Hz than at 2 Hz. 8-Hydroxy-2-(di-n-propylamino)tetralin did not alter the evoked overflow. The inhibitory effect of 5-HT or 5-OCH3-T was antagonized by metitepin but not affected by ketanserin or rauwolscine.
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2.
In pithed rats 5-HT and 5-OCH3-T by themselves dose-dependently increased heart rate. The positive chronotropic effect of 5-HT 10 μmol/kg, which was not affected by ketanserin, was considerably decreased by desipramine, indicating that 5-HT at least at this high dose acts predominantly by a tyramine-like indirect sympathomimetic effect. The tachycardic response to 5-OCH3-T was reversed to a very slight negative chronotropic effect by ketanserin or methysergide, but was not affected by desipramine or propranolol indicating that the increase in heart rate induced by 5-OCH3-T is mediated via 5-HT2-receptors on the pacemaker cells.
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3.
Ketanserin-treated pithed rats were used to study the effect of 5-OCH3-T on the tachycardia induced by stimulation of the preganglionic sympathetic nerves via the pithing rod. The nerve stimulation-induced tachycardia was inhibited by 5-OCH3-T to a significantly higher extent than the tachycadia induced by infusion of noradrenaline. The inhibitory effect of 5-OCH3-T on nerve stimulation-induced tachycardia could not be antagonized by metitepin or rauwolscine; it decreased with increasing frequency of stimulation.
It is concluded that the sympathetic nerves of the rat vena cava are endowed with inhibitory presynaptic 5-HT1 receptors. Most of the data obtained in the pithed rat suggest that such receptors also appear to be present on the sympathetic nerves supplying the sinus node, and that they are operative in vivo.
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This study was supported by a grant of the Deutsche Forschungsgemeinschaft
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Göthert, M., Schlicker, E. & Kollecker, P. Receptor-mediated effects of serotonin and 5-methoxytryptamine on noradrenaline release in the rat vena cava and in the heart of the pithed rat. Naunyn-Schmiedeberg's Arch. Pharmacol. 332, 124–130 (1986). https://doi.org/10.1007/BF00511401
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DOI: https://doi.org/10.1007/BF00511401