REGIONAL 5-HYDROXYINDOLEACETIC ACID PRODUCTION IN HUMANS

Veno-arterial plasma concentration differences and regional organ plas ma flows were used to quantify the relative amounts of 5-hydroxyindole acetic acid (5-HIAA) contributed by various sites into the peripheral circulation. Positive venoarterial concentration gradients were found in the hepatosplanchnic, forearm, cardiac and jugular vessels in the h ealthy subjects. The renal circulation was determined to be the princi pal site of 5-HIAA clearance, extracting 18 +/- 2 nmo/min. The gut was the greatest contributor to the total 5-HIAA plasma pool with the rel ative contributions of the various organs being as follows: hepatospla nchnic organs 58 %, skeletal muscle 26 %, brain 6 % and the heart 3 %. The source of 5-HIAA stemming from these regional beds remains unknow n, it may derive from serotonin taken up by and deaminated in ubiquito us endothelial cells, enterochromaffin cells of the gut, peripheral se rotonergic nerves, serotonin turnover in platelets or perhaps the meta bolism of serotonin taken up by sympathetic nerves. To test the latter hypothesis we examined 23 patients with chronic congestive heart fail ure and 9 patients with pure autonomic failure to investigate the poss ible effects of sympathetic nervous system overactivity and underactiv ity on peripheral 5-HIAA production and plasma 5-HIAA concentration. T he resting arterial plasma 5-HIAA concentration in the heart failure p atients was increased three-fold. This elevated plasma 5-HIAA concentr ation was attributable to an increased rate of whole body 5-HIAA produ ction. The arterial 5-HIAA plasma concentration in the autonomic failu re patients was paradoxically elevated, being 70 % greater than that o f the healthy subjects. The increased 5-HIAA plasma concentration in t hese patients was accounted for by a reduction in 5-HIAA plasma cleara nce. In all subjects studied there was a weak relationship only betwee n total body norepinephrine spillover to plasma and the arterial 5-HIA A plasma concentration. We found that in healthy subjects the overflow of 5-HIAA into the hepatic vein was significantly related to the unde rlying degree of sympathetic activity. It can be concluded that 5-HIAA is produced at a number of sites throughout the body with the arteria l plasma concentration being dependant on both the level of production and plasma clearance. By far the majority of 5-HIAA in plasma is deri ved from the gut with only minimal contribution from the brain.