5-Hydroxytryptamine (5-HT;
serotonin)-containing neurones contribute to reflex activation of parasympathetic outflow in a number of species, but the
5-HT receptors mediating these effects have yet to be fully determined. The present experiments demonstrate that central 5-HT7 receptors are involved in the vagal
bradycardia evoked during the cardiopulmonary reflex, baroreflexes and the chemoreflex, as well as other autonomic changes caused by these reflexes. The experiments examined the effects of the selective
5-HT7 receptor antagonists
SB-269970 and SB-656104 on these reflexes. For the cardiopulmonary reflex, when compared to time-matched vehicle control experiments, intracisternal application of
SB-269970 (30-300 microg kg(-1), i.c.) dose-dependently attenuated the evoked
bradycardia. At the highest dose,
SB-269970 also attenuated the reflex
hypotension and sympathoinhibition. The structurally different
5-HT7 receptor antagonist SB-656104 (100 microg kg(-1), i.c.) similarly attenuated the reflex
bradycardia and
hypotension.
SB-269970 (100 microg kg(-1), i.c.) also attenuated the
bradycardias evoked by electrical stimulation of aortic nerve afferents and the baroreflex evoked by the pressor response to
phenylephrine (3-25 microg kg(-1), i.v.). The gain of the baroreflex was also significantly attenuated (0.15 +/- 0.06 versus 0.34 +/- 0.06 ms mmHg(-1)). Finally,
SB-269970 (100 microg kg(-1), i.c.) significantly attenuated both the
bradycardia and sympathoexcitation evoked by the chemoreflex. These data indicate that central 5-HT7 receptors play an important facilitatory role in the reflex activation of vagal outflow to the heart.