We developed and applied new techniques for assessing sympathoadrenomedullary function at rest, during stress, and in disease states by using levels of the sympathetic neurotransmitter norephinephrine (NE), the hormone epinephrine (E), the catecholamine precursor dihydroxyphenylalanine (DOPA), and the norepinephrine metabolite dihydroxypehenylglycol (DHPG) to indicate various aspects of neurotransmitter synthesis, release, re-uptake, and metabolism. A pharmacokinetic approach including systemic intravenous infusions of tracer-labelled NE and isoproterenol was used to discover that changes in total body spillover of NE Into arterial blood provided better agreement with sympathetically-mediated cardiovascular responses during mental challenge than did measurements of changes in antecubital venous or arterial NE. The heart was found to be particularly dependent on neuronal uptake for removal of NE. Techniques were developed to provide in vivo estimates of NE levels at post- synaptic adrenoceptors and at neuronal uptake sites. Plasma DPPG was found to indicate intraneuronal disposition of axoplasmic NE. DOPA in the bloodstream was found to emanate from sympathetic nerves and to provide a major source of dopamine (DA) production in the kidney. Changes in plasma DOPA appeared to indicate changes in the rate of catecholamine biosynthesis. Sympathoneural and adrenomedullary activity were found to be regulated differentially during various stresses. Positron emission tomography is being studied as a possible means to visualize sympathetic function. A large number of collaborative studies about catechols are summarized.
