EFFECTS OF 5-HYDROXYTRYPTAMINE AND RELATED COMPOUNDS ON THE SYMPATHETIC-NERVES OF THE RABBIT HEART

In isolated rabbit hearts perfused with Tyrode solution we investigated the effects of various mono- and dihydroxytryptamines on the noradrenaline release from (and uptake into) the terminal sympathetic nerve fibres. The noradrenaline in the perfusate was estimated spectrofluorimetrically. Alterations of heart rate were also determined. 1. 5-Hydroxytryptamine (5-HT), 6-hydroxytryptamine (6-HT) and 5,7-dihydroxytryptamine (5,7-DHT) inhibited the uptake of exogenous noradrenaline from the perfusion fluid into the sympathetic nerves. 2. Continuous perfusion of hearts with 6-HT caused a gradual increase in noradrenaline release and heart rate. Desipramine abolished both the noradrenaline-releasing and the positive chronotropic effects, whereas pindolol inhibited only the increase in heart rate. Perfusion of hearts with 5-HT before and during bolus injection of 6-HT did not alter the positive chronotropic effect of 6-HT. 3. Continuous perfusion of hearts with 5-HT, 5,7-DHT or 5,6-dihydroxytryptamine (5,6-DHT) rapidly induced a release of high amounts of noradrenaline and/or a pronounced increase in heart rate which returned to slightly elevated levels within the first 4 min of perfusion with these indolethylamines. 4. Bolus injection of tryptamine, 5-HT,7-hydroxytryptamine (7-HT), 5,6-DHT or 5,7-DHT caused a noradrenaline release and a positive chronotropic effect which attained a maximum within the first 2 min after injection, whereas 4-hydroxytryptamine and 6,7-dihydroxytryptamine were ineffective. 5. The 5-HT- or 5,7-DHT-induced noradrenaline release was not decreased by desipramine, methiothepin, methysergide and pindolol. However, the latter compound inhibited the positive chronotropic effects evoked by the indolethylamines. 6. Reserpine pretreatment, cocaine, mianserin, verapamil or 5-HT (infused into the aortic cannula before and during injection of 5-HT or 5,7-DHT) decreased the noradrenaline-releasing effect of the indolethylamines. 7. Dose-response curves were established for the positive chronotropic effects induced by tryptamine, 5-HT, 7-HT, 5,6-DHT and 5,7-DHT. In addition, concentration-response curves were determined for the inhibitory effects of there compounds on the 5-HT-induced increase in heart rate. There was a good correlation between the negative logarithms of the ED50 and IC50 values of the indolethylamines (r=0.99); the slope of the regression line was about 1. These findings confirm that the positive chronotropic effects of indolethylamines on the rabbit heart are due to noradrenaline release. Whereas 6-HT appears to cause its indirect sympathomimetic effect by a tyramine-like mechanism, the other compounds induce noradrenaline release by activation of presynaptic 5-HT receptors on the terminal sympathetic nerve fibres. © 1979 Springer-Verlag.