REGIONAL HOMOVANILLIC-ACID PRODUCTION IN HUMANS

Peripheral plasma levels of homovanillic acid (HVA), the deaminated an d o-methylated metabolite of dopamine, are often used as an indicator of central nervous system dopaminergic activity. Using percutaneously placed catheters, we studied the regional inputs into the plasma HVA p ool in 60 healthy volunteers. Veno-arterial differences and organ plas ma flows were used to quantify the relative amounts of HVA contributed by various sites into the peripheral circulation. Positive arterio-ve nous HVA gradients were found in the pulmonary, hepatosplanchnic, skel etal muscle and jugular vessels of the normal volunteers. No HVA incre ment was found in the coronary sinus. The renal circulation was determ ined to be the principal site of HVA clearance, extracting 27 nmol/min . The regional contributions of HVA were as follows: lungs 21 nmol/min , hepatosplanchnic organs 3 nmol/min, skeletal muscle 3 nmol/min and t he brain 4 nmol/min. The pattern of regional HVA production contrasted with that of the deaminated dopamine metabolite, dihydroxyphenylaceti c acid, for which the heart was the principal site of production ident ified. Sixteen patients with chronic congestive heart failure (CHF) an d 6 patients with pure autonomic failure (PAF) were also studied to in vestigate possible effects of sympathetic nervous system overactivity and underactivity on peripheral HVA production and plasma HVA concentr ation. The resting arterial plasma HVA concentration in CHF was increa sed approximately 3-fold. Unexpectedly, this was attributable to reduc ed HVA plasma clearance, not increased HVA production. Total HVA produ ction in PAF was diminished by 40 %. PAF patients had normal resting a rterial HVA levels, this being accounted for by a 57 % fall in the ren al plasma clearance of HVA. Acute sympathetic nervous system activatio n in response to bicycle riding was accompanied by a 34 % increase in the arterial concentration of HVA. It can be concluded that HVA is pro duced at a number of sites throughout the body not renowned for their dopaminergic innervation. Regional HVA production is associated, in pa rt, with the metabolism of precursor dopamine in sympathetic nerves an d at a rate which appears to be influenced by sympathetic nervous acti vity. To obtain an accurate indication of central dopaminergic activit y the confounding influences of HVA plasma clearance and peripheral HV A production must be excluded.