SYMPATHOADRENAL FUNCTION IN HEALTH AND DISEASE

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The sympathoadrenal system is one of the most powerful and rapidly-acting of the body's "stress" systems. Our goals have been to understand better how this system is regulated, how its function is integrated with that of other systems contributing to the maintenance of the internal environment, and whether and how it plays a pathophysiologic role in neurocardiologic diseases. During the past year we developed positron emission tomographic (PET) scanning to provide the first non-invasive, in vivo means to examine cardiac sympathetic innervation and function. We also developed in vivo microdialysis to examine relationships between concentrations of neurotransmitters in the brain and sympathoadrenal outflow. The microdialysates will be analyzed by a new multi-electrode array detector (neurochemical analyzer). We obtained further evidence suggesting a relationship between endogenous plasma dopa and biosynthesis of the sympathetic neurotransmitter, norepinephrine (NE), and noted abnormally increased urinary excretion of dopa in patients with salt-sensitive hypertension. We used a method including direct sympathetic nerve recording to examine pre-synaptic actions of anti-hypertensive drugs in vivo. The close relationship between sympathetic nerve activity and regional release of NE into the bloodstream was confirmed in humans and rats. We obtained evidence of sympathoadrenal hyperreactivity, as indicated by a yohimbine challenge test, in some patients with hypertension; demonstrated by microdialysis that yohimbine releases NE in the brain in rats; and showed by direct nerve recording that yohimbine increases sympathetic nerve traffic and augments regional release of NE in the heart and limbs in humans. PET scanning, neurochemical analysis, and direct sympathetic nerve recording can be used to answer long-standing questions about the role of the sympathoadrenal system in health, stress, and disease.