Received October 18, 2004
Revised November 15, 2004
Accepted after revision November 23, 2004

¹ Royal Free & University College Medical School

^* To whom correspondence should be addressed. E-mail: d.jordan{at}rfc.ucl.ac.uk.

	Abstract

Cardiac vagal preganglionic neurones (CVPNs) are located within the dorsal vagal nucleus (DVN) and the nucleus ambiguus (nA). In mammals, nA vagal preganglionic neurones have small myelinated axons and mediate major chronotropic effects, those in DVN having non-myelinated axons and mediating smaller chronotropic, dromotropic and inotropic effects. Numerous studies demonstrate important influences of serotonin (5-HT) at multiple sites controlling autonomic outflows including nucleus tractus solitarius (NTS) where cardiorespiratory afferent fibres terminate, the CVPNs and rostral ventrolateral medulla (RVLM) - location of sympathetic premotor neurones. We have demonstrated roles for some of the numerous 5-HT receptor subtypes (5-HT₁, 5-HT₂, 5- HT₃, 5-HT₄ and 5-HT₇) in brainstem regions involved in cardiac control. Intracisternal application (i.c.) of selective ligands was used to study the effect of 5-HT receptors on heart rate and its reflex control. Further electrophysiological studies were also carried out to delineate their location and mechanisms of action of these ligands. Blocking 5-HT_1A receptors attenuated bradycardias evoked by stimulating baroreceptor and cardiopulmonary afferents but not arterial chemoreceptors whereas antagonising 5- HT₇ receptors markedly attenuated all these reflex bradycardias. Within the DVN, nA and NTS activation of 5-HT_1A receptors could excite or inhibit neurones. In NTS 5-HT₂ receptors also had variable effects, 5-HT_2B receptors excite and 5-HT_2C receptors inhibit. Antagonism of 5-HT₃ receptors attenuated upper airway and cardiopulmonary reflex bradycardias - compatible with data showing that 5-HT₃ receptors excite DVN and NTS neurones by a glutamate dependent mechanism. The origin of the glutamate (neuronal or glial) remains unresolved but glia are a possibility since baro-sensitive NTS neurones receive few direct 5-HT containing synaptic contacts. Thus, 5-HT plays a critical role in the control of vagal outflow to the heart, however, why so many different receptors are involved, and their relative functional roles remains unresolved.

Key Words: 5-Hydroxytryptamine, Heart, Vagus