Central Serotonergic Control of Cardiovascular Reflexes

Central serotonergic neurones control reflex parasympathetic outflow to the heart, airways and bladder in a number of species, and different 5-HT receptor subtypes are involved in this effect. 5-HTja and 5 -HT3 receptors in the brainstem facilitate these reflexes, whilst 5-HTjb/id, 5-HT2 and 5 -HT4 receptors inhibit them. Recently, central 5 -HT7 receptors have been implicated in bladder reflexes. Experiments on anaesthetised rats showed that the selective 5-HT7 receptor antagonists SB-269970 and SB-656104, given intracistemally (i.e.), attenuated cardiopulmonary, baroreflex and chemoreflex bradycardias. Similarly, the selective 5-HTia receptor antagonist WAY-100635 attenuated cardiopulmonary and chemoreflex (but not baroreflex) bradycardia, whilst robalzotan and (-)-pindolol (antagonists at 5-HT 1 a receptors) had no effect on cardiopulmonary and baroreflex bradycardias respectively. Chemical stimulation of presumed^ serotonergic cell bodies in raphe magnus/pallidus evoked a bradycardia that could not be attenuated either by 5-HT receptor antagonists (given i.v.) or by prior 5-HT depletion. The latter did, however, significantly attenuate cardiovascular reflex sensitivity. Activation of nucleus tractus solitarius (NTS) neurones by the vagus was inhibited by the iontophoretic AMPA receptor antagonist DNQX or by topical SB-269970. Subsequent histology suggested that 5-HT containing terminals do not make close appositions with these neurones. Preliminary data demonstrate that SB-269970 (given i.e.) effectively attenuates the cardiopulmonary reflex in awake rats, but has variable effects on the chemoreflex. The data suggest that 5-HT7 receptors in the NTS are crucially involved in the central transmission of reflex bradycardias, at least in rats. The role of the 5-HTia receptor is less clear-cut than in the rabbit, and may reveal a species difference. The origin of 5HT activating these receptors is unlikely to be the medullary raphe neurones, but may be primary afferents terminating in the NTS. Since recent ultrastructural evidence shows 5-HT terminals and NTS cardiovascular neurones are often separated by astroglial leaflets, astrocytes may be involved in serotonergicglutamatergic signalling.