The C1 area of rostral ventrolateral medulla: a central site integrating autonomic responses to hemorrhage.

Activation of the sympathetic neurons and release of adrenomedullary catecholamines are the principal early reflex responses to hemorrhage. These are initiated by arterial baro- and chemoreceptors, from other cardiopulmonary receptors, and by intracerebral receptors responding to ischemia. A principal gateway for integrating the autonomic responses are a small collection of neurons in a region of the rostral ventrolateral medulla (RVL), containing a cluster of neurons of the C1 adrenergic cell group, the C1 area. Neurons in the C1 area of RVL project exclusively to autonomic nuclei of the spinal cord, are tonically active, and fire with a rhythm linked to the cardiac cycle. They are essential for maintaining resting discharge of sympathetic nerves and, consequently, arterial pressure (AP) and heart rate. They also are critical for reflex changes in AP in the baro- and chemoreceptor, somato-sympathetic (pain), and cerebral ischemic reflexes. Neurons of the C1 area are under tonic excitatory and inhibitory control by pathways from other autonomic centers. They are controlled by a range of neurotransmitters including, gamma aminobutyric acid (GABA), acetylcholine, catecholamines, enkephalin, and several neuropeptides. They also serve as a site of action for the hypotensive actions of several clinically important neurotransmitters. The C1-area of RVL may play a critical role in the autonomic responses to hemorrhage and may be an important target for drugs seeking to treat hemorrhagic shock.