In summary: satellite symposium on central alpha-adrenergic blood pressure regulating mechanisms

This symposium reviewed the fundamental principles, pharmacology, and clinical pharmacology of central alpha-adrenergic blood pressure regulating mechanisms. Fundamental principles Arterial baro- and chemoreceptor signals reach the nucleus of the tractus solitarius (NTS) via vagal and glossopharyngeal afferents. The NTS communicates with sympathetic preganglionic neurons in the spinal cord via centers and tracts in the medulla, pons, and hypothalamus that include an alpha-adrenergic inhibitory network. Descending tracts emphasized in this symposium originate in the C-1 epinephrine cells of the medulla, B-1 and B-3 serotonin cells of the medulla, and A-5 norepinephrine cells of the pons. Transmitters involved are norepinephrine, epinephrine, serotonin, glutamate, and gamma-aminobutyric acid (GABA). Catecholamine enzymes share protein domains in their primary structures and may be coded by linked or single genes. New methods of purifying and locating alpha- and beta-receptors have been developed. Pharmacology Methyldopa, clonidine, and clonidine-like drugs lower blood pressure by stimulating postsynaptic alpha 2-receptors in a brain stem inhibitory network, which down-regulates these receptors. Alpha 1-receptors were found to be higher in normotensive than in hypertensive rats and were increased in the latter by methyldopa administration. Alpha 2-receptors were found to differ in various tissues, which permits the development of highly selective agonists and antagonists. Although alpha-methylnorepinephrine is probably the principal metabolite of methyldopa, alpha-methylepinephrine and alpha-methyldopamine may also contribute. The site of action usually is identified as the NTS. Possible roles for the descending tracts were suggested. Clinical pharmacology Methyldopa, clonidine, guanfacine, and related drugs lower blood pressure principally by CNS mechanisms but peripheral actions may also contribute.(ABSTRACT TRUNCATED AT 250 WORDS)