EFFECTS OF CARBIDOPA AND OF INTRAVENOUS SALINE INFUSION INTO NORMAL AND HYPERTENSIVE SUBJECTS ON URINARY FREE AND CONJUGATED DOPAMINE

Objective To investigate the possible role played by endogenous dopami ne as a modulator of renal sodium (Na+) reabsorption after a combined Na+ and volume load. Design A randomized placebo-controlled study. Met hods Ten healthy volunteers and four hypertensive patients were subjec ted to intravenous infusions of 2 l 0.9% saline (308 mmol Na+) adminis tered from 1000 to 1300 h after oral administration of placebo or of c arbidopa, a dopamine decarboxylase inhibitor. Results Studies on contr ol subjects after placebo showed that natriuresis occurred during the 6 h after commencement of the saline infusion, with falls in plasma al bumin concentration, plasma renin activity and plasma aldosterone conc entration; in comparison with results of mock infusion (6 mmol Na+) th ere was no change in the urinary excretion of dopamine and noradrenali ne (in their free or conjugated forms). There was, however, a marked s urge in excretion of urinary conjugated dopamine and in the dopamine: noradrenaline ratio from 1300 to 1600 h, after either type of infusion . Administration of carbidopa before the saline infusion resulted in a marked decrease in excretion of urinary free dopamine, but had no eff ect on the surge in excretion of urinary conjugated dopamine. Saline i nfusion decreased proximal fractional Na+ reabsorption. Administration of carbidopa delayed but did not prevent this decrease. The effects o f saline infusion and of carbidopa on the urinary excretion of dopamin e and noradrenaline from hypertensive patients were similar to those o bserved with the healthy volunteers. Conclusions These findings indica te that volume expansion by intravenous saline infusion has no appreci able effect on the urinary free dopamine excretion from normal or hype rtensive humans; with any apparent increase, it is important to exclud e the possibility of conversion of conjugates to free dopamine in vitr o. Furthermore, that carbidopa administration did not inhibit the afte rnoon surge of conjugated dopamine suggests that administration of car bidopa is deficient as a tool to investigate the functional role of th e renal dopamine system.