The intracerebroventricular (i.c.v.) injection of
serotonin (5-HT) increases blood pressure and decreases heart rate (HR) in conscious rats by activation of 5-HT2/1C receptors. Since the
bradycardia is eliminated by pretreatment with a ganglionic or V1-vasopressin antagonist, we proposed that the decrease in HR results from an effect on cardiac autonomic activity which is potentiated by
vasopressin. The present study aimed first, to further characterize mechanisms by which the i.c.v. injection of
5-HT (2.5 micrograms) decreases HR in conscious rats, and second to determine the cardiovascular responses to
5-HT (2.5 micrograms, i.c.v.) in rats with chronic sinoaortic deafferentation (SAD). In intact rats, the
bradycardia elicited by
5-HT was eliminated by a combination of the
muscarinic antagonist atropine and the
beta-adrenoceptor antagonist sotalol; neither antagonist was effective alone. In rats with SAD,
5-HT produced a larger increase in blood pressure and a marked
tachycardia, both of which were eliminated by the 5-HT2/1C antagonist
LY 53857. Furthermore, in rats with SAD the 5-HT-induced increase in HR was blocked by
sotalol alone. In conclusion,
5-HT (2.5 micrograms, i.c.v.) acts on central 5-HT2/1C receptors to increase arterial pressure. In intact rats this decreases HR by
vasopressin-potentiated activation of baroreceptor reflexes and subsequent increase in vagal tone and decrease in cardiac sympathetic tone. In the absence of baroreflexes, a direct central effect of
5-HT to produce a beta-
adrenoceptor-mediated cardioacceleration is unmasked.