Receptor-mediated effects of serotonin and 5-methoxytryptamine on noradrenaline release in the rat vena cava and in the heart of the pithed rat

Abstract

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. 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. In pithed rats 5-HT and 5-OCH3-T by themselves dose-dependently increased heart rate. The positive chronotropic effect of 5-HT 10 mumol/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.(ABSTRACT TRUNCATED AT 250 WORDS)