Central monoamine neurons and cardiovascular control.

This review discusses the cardiovascular actions of central noradrenergic and serotonergic neurons, particularly with respect to the mechanism of action of the centrally acting antihypertensive agents clonidine, methyldopa (alpha-MD) and rilmenidine. The predominant actions of the noradrenergic neurons in the brainstem are to inhibit vasomotor and cardiac sympathetic activity and to facilitate cardiac vagal responses. By contrast the serotonergic neurons in the brainstem increase blood pressure and heart rate through excitation of cardiac and vasomotor sympathetic pathways and inhibition of the cardiac vagus nerve. The centrally acting antihypertensive drugs clonidine, rilmenidine and alpha-MD activate these noradrenergic pathways and inhibit the serotonergic pathways. Noradrenergic projections to the spinal cord tonically inhibit while the serotonergic neurons facilitate sympathetic vasomotor tone. In combination with other spinally projecting pathways, these monoamine fibers form part of a high gain control system for responding to changes in specific afferent information. However, the spinal pathways do not contribute to the actions of clonidine or alpha-MD. The forebrain noradrenergic projections are important for the noradrenergic baroreflex vagal facilitation produced by acute 6-OHDA and methyldopa, but not clonidine. By activating this forebrain pathway methyldopa minimises the baroreflex compensation that might normally be expected following a reduction in blood pressure.