In Summary: Satellite Symposium on Central α-Adrenergic Blood Pressure Regulating Mechanisms

Abstract

This symposium reviewed the fundamental principles, pharmacology, and clinical pharmacology of central α-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 α-adrenergic inhibitory network. Descending tracts emphasized in this symposium originate in the C-l epinephrine cells of the medulla, B-l and B-3 serotonin cells of the medulla, and Α-5 norepinephrine cells of the pons. Transmitters involved are norepinephrine, epinephrine, serotonin, glutamate, and gammα-aminobutyric acid (GABA). Catecholamine enzymes share protein domains in their primary structures and may be coded for by linked or single genes. New methods of purifying and locating α-and β-receptors have been developed. Pharmacology Methyldopa, clonidine, and clonidine-like drugs lower blood pressure by stimulating postsynaptic α 2 -receptors in a brain stem inhibitory network, which down-regulates these receptors. α 1 -receptors were found to be higher in normotensive than in hypertensive rats and were increased in the latter by methyldopa administration. α 2 -receptors were found to differ in various tissues, which permits the development of highly selective agonists and antagonists. Although α-methylnorepinephrine is probably the principal metabolite of methyldopa, α-methylepinephrine and α-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. Growth hormone concentrations do not increase in hypertensive patients with central α-agonist administration. In animal and clinical studies, the withdrawal reaction was prominent with clonidine, modest with guanfacine, and negligible with methyldopa. Related were decreases in central α 2 -receptors and rapid eye movement, or REM, sleep. Blood pressure lowering is brought about by balanced reductions in peripheral vascular resistance and cardiac output with preservation of blood flow to vital organs. Reversal of left ventricular hypertrophy in animals without loss of contractility was demonstrated at antihypertensive doses with methyldopa. The beneficial influence of methyldopa and other agents on the natural history of hypertension was described in a report on 15 years of experience.