SYMPATHOADRENAL AND CATECHOLAMINERGIC FUNCTION IN HEALTH AND DISEASE

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Our Section develops and applies methods for assessing the function of central and peripheral catecholaminergic systems and the coordination of these systems with other homeostatic systems in health, stress, and disease. Findings this year include: (1) positron emission tomographic (PET) scanning after systemic administration of 6-[18F]fluorodopamine ([18F]-6F-DA) provided a noninvasive, in vivo means to examine cardiac sympathetic innervation and function in humans, with acceptable absorbed radiation doses.(2) Clinical microneurographic and neurochemical methods were used to demonstrate gluco-corticoid-induced sympathoinhibition in humans, to describe a distinctive neurochemical pattern in Menkes disease, to localize the site of sympathetic neuroeffector dysfunction in multiple system atrophy, to determine whether patients with Fabry's disease have sympathetic neuropathy, to test the "epinephrine hypothesis" of sympathetic neurotransmission, to document clozapine~induced noradrenergic stimulation, and to test for the presence of functional beta-adrenoceptors and angiotensin II receptors on sympathetic terminals in the human forearm. (3) Assays for plasma levels of O~methylated metabolites of catecholamines were developed and validated, and measurements of plasma levels of metanephrines were found to provide superior neurochemical means to diagnose pheochromocytoma, a catecholamine-secreting tumor. (4) Comprehensive measurements of concentrations of norepinephrine and dopamine and their metabolites in swine and sheep provided evidence for substantial production and metabolism of dopamine in porcine mesenteric organs and for non~neuronal catecholamine biosynthesis in ovine lungs. The renal DOPA~DA system is another "atypical" catecholaminergic system, and the possibility of abnormal function of this system in salt~sensitive hypertension is being explored, as well as treatment with L~DOPA as a renal dopaminergic prodrug in congestive heart failure.