Autonomic nervous system activity is essential for maintaining circulatory and metabolic homeostasis. In order to study sympathetic nervous system function and its relationship to other neuroendocrine systems, it is necessary to measure neurotransmitter, hormonal, and peptide levels in response to various stimuli. The levels of norepinephrine, epinephrine, and dopamine and their metabolites in various body fluids reflect the activity of the neurones from which these neurotransmitters are released. Cerebrospinal fluid levels of monoamine metabolites, enzymes related to neurotransmitter synthesis and degradation, and peptides can be used to assess central nervous system neurotransmitter/neuropeptide function and metabolism. It is necessary to consider the origin of these metabolites to make appropriate corrections for valid interpretations of the data. These strategies have been used to study patients with neurogenic orthostatic hypotension and other disorders in which abnormal adrenergic function is suspected. Plasma NE increases following intravenously administered acetylcholine in normal subjects. Lack of an increase in patients with pure autonomic failure (PAF) is consistent with post-ganglionic sympathetic neuronal dysfunction. Patients with multiple system atrophy (MSA) may develop depolarization blockade due to cholinergic receptor supersensitivity since they manifest an exaggerated response at low doses followed by a return of plasma NE to baseline levels. Only patients with PAF have beta-adrenergic receptor supersensitivity. Increases in plasma norepinephrine and renin activity following isoproterenol administration in normal subjects may result from reflex cardiovascular and renal mechanisms. Diminished sweat production to intradermal methacholine in patients with autonomic failure suggests that human sweat glands do not develop denervation supersensitivity. Cerebrospinal fluid immunoreactivity to rat locus coeruleus suggests that degeneration in MSA may release antigens that induce antibodies against neurons in selected brain regions. Structural and metabolic brain abnormalities defined by neuroimaging studies facilitate clinical distinction between PAF and MSA. Improve in producing abnormalities of neurotransmitter metabolism and peptide function in these clinical disorders leads to more rational therapeutic approaches.
