Involvement of 5-HT in Cardiovascular Afferent Modulation of Brainstem Circuits Involved in Blood Pressure Maintenance

Stimulation of all the major cardiovascular reflexes causes the release of 5-hydroxytryptamine (5-HT) in nucleus tractus solitarii (NTS) and the nucleus ambiguus. At present the experimental evidence indicates that the major receptor subtypes involved are 5-HT3, 5-HT1A, 5-HT2, and 5-HT7. In the NTS 5-HT3 receptor activation increases the release of glutamate from the terminals of afferent fibers. In this respect 5-HT3 antagonists were found to attenuate the excitation of NTS neurones by these afferents and are involved in eliciting the cardiovascular changes caused by the diving response and the cardiopulmonary reflex. 5-HT3 receptors can also activate GABAergic pathways and this action is more prominent when the agonists are given by microinjection into the NTS. Activation of 5-HT1A receptors in the NTS can have either excitatory or inhibitory effects. Blockade of these receptors does not seem to have an influence on the excitation of NTS neurones by afferents, making their physiological role unclear. However, 5-HT1A receptors do play a physiological role in reflex excitation of cardiac vagal preganglionic neurones located in the nucleus ambiguus. 5-HT2 receptors, mainly 2A, are excitatory and one of their major effects is to cause sympathoexcitation. This does not apply to the sympathetic outflow to heart. Their physiological role in these pathways remains unclear. Blockade of 5-HT7 receptors attenuates the cardiovascular changes caused by all cardiovascular reflexes tested and these receptors are involved in the excitation of NTS neurones by afferents. The lack of selective agonists for 5-HT7 receptors makes it difficult to determine their precise physiological role. Overall it is clear that 5-HT is important for the regulation of these pathways, but the exact role and the interactions of the effects caused by activation of the different receptor subtypes remains unclear