5-hydroxytryptamine inhibits the tachycardia induced by selective preganglionic sympathetic stimulation in pithed rats

It has been shown in several species that serotonin (5-hydroxytryptamine; 5 -HT) is able to inhibit the responses produced by sympathetic stimulation i n a wide variety of blood vessels and other organs, including the heart. Ho wever, in pithed rats, the analysis of potential sympatho-inhibitory action s of 5-HT is hampered by the fact that 5-HT (given as i.v, bolus injections ) produces tachycardia per se. Moreover, most studies have investigated 5-H T-induced sympatho-inhibition at only one frequency of stimulation. Thus, t he present study set out to find the experimental conditions to overcome th ese problems. In this regard, we analyzed the potential ability of 5-HT, ad ministered as i.v. continuous infusions, to inhibit the tachycardia caused by stimulation of the preganglionic (C-7-T-1) sympathetic outflow in pithed rats. Sympathetic cardiostimulation (0.01-3 Hz) resulted in frequency-depe ndent increases in heart rate; these responses were potentiated after desip ramine (50 mu g/kg, i.v.). During continuous infusions of 5-HT (3.1-10 mu g /kg.min, i.v.), but not saline, the sympathetically-induced tachycardia was dose-dependently inhibited in both control and desipramine-pretreated rats . This inhibitory effect of 5-HT was significantly more pronounced at lower frequencies of stimulation. In contrast, the above infusions of 5-HT did n ot inhibit the tachycardia induced by i.v. bolus injections of noradrenalin e in both control and desipramine-pretreated rats. Taken together, the abov e findings confirm that 5-HT induces inhibition of the sympathetic chronotr opic outflow in the rat by acting at receptors located prejunctionally, wit hout evoking tachycardia, over a wide range of stimulation frequencies.