Reis DJ, Morrison S, Ruggiero DA
Division of Neurobiology,
Cornell University Medical College,
New York, New York 10021
Recent studies have demonstrated that the neurons of the lower brainstem that are responsible for maintaining normal levels of arterial pressure reside in a specific area of the rostral ventrolateral medulla. In rat, the critical zone corresponds to a small region containing a subpopulation of the adrenergic C1 group, defined immunocytochemically by the presence of the epinephrine-synthesizing enzyme phenylethanolamine N-methyltransferase. Neurons of this region (the C1 area), possibly including the adrenergic neurons, directly innervate preganglionic neurons in the spinal cord, and are tonically active and sympathoexcitatory. The excitatory transmitter released into the spinal cord is unknown. The discharge of C1 area neurons is locked to the cardiac cycle and, in turn, leads to firing of sympathetic preganglionic neurons. The C1 area neurons are inhibited by baroceptor input and mediate the vascular component of baroceptor reflexes. They also mediate somato-sympathetic pressor responses from skin and muscle and participate in reflex responses to hypoxia. The neurons are directly innervated by local neurons containing gamma-aminobutyric acid, acetylcholine, enkephalin, and substance P, all of which modulate arterial pressure. The C1 area is the site of the hypotensive actions of clonidine. Clonidine appears to act on imidazole receptors in the C1 area to lower arterial pressure. The natural ligand for these receptors may be a newly defined substance in brain, clonidine-displacing substance. Neurons of the C1 area appear to be the critical neuronal group governing the normal resting and reflex control of arterial pressure. They may play a critical role in the maintenance of elevated arterial pressure in hypertension and as a site of action of antihypertensive drugs.