Kellett, D.O.; (2005) Central serotonergic control of cardiovascular reflexes. Doctoral thesis , University of London.

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Abstract

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-HTiA and 5-HT3 receptors in the brainstem facilitate these reflexes, whilst 5-HTiB/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 intracisternally (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-HTiA 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 AMP A 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 5-HT 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 serotonergic-glutamatergic signalling.

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