The Mechanistic Basis of Centrally Active Antihypertensive Drugs*

Antihypertensive drugs lower arterial blood pressure by decreasing cardiac output, total peripheral resistance, or both. Most of the drugs act at the level of the heart, blood vessel, kidney, and/or the autonomic nervous system. One class selectively acts in the central nervous system. These drugs act mainly at the level of the brainstem to decrease central sympathetic outflow. Neurons in the rostral ventrolateral medullary (RVLM) pressor area are tonically active and drive the activity of sympathetic preganglionic neurons located in the intermediolateral cell column of the thoraco-lumbar spinal cord. In turn, these preganglionics then activate the postganglionic sympathetic neurons and release norepinephrine onto the heart and blood vessels to increase arterial pressure. Neurons in the RVLM are predominantly modulated by two other medullary nuclei: the nucleus of the solitary tract (involved in baro- and chemoreceptor pathways) and the caudal ventrolateral medullary (CVLM) depressor area. These three main medullary areas co-ordinate sympathetic outflow and are the targets of many centrally acting antihypertensive drugs.