title: Effects of carbidopa and of intravenous saline infusion into normal and hypertensive subjects on urinary free and conjugated dopamine.
abstract: OBJECTIVE
  To investigate the possible role played by endogenous dopamine as a modulator of renal sodium (Na+) reabsorption after a combined Na+ and volume load.
  
  
  METHODS
  A randomized placebo-controlled study.
  
  
  METHODS
  Ten healthy volunteers and four hypertensive patients were subjected to intravenous infusions of 21 0.9% saline (308 mmol Na+) administered from 1000 to 1300 h after oral administration of placebo or of carbidopa, a dopamine decarboxylase inhibitor.
  
  
  RESULTS
  Studies on control subjects after placebo showed that natriuresis occurred during the 6 h after commencement of the saline infusion, with falls in plasma albumin concentration, plasma renin activity and plasma aldosterone concentration; in comparison with results of mock infusion (6 mmol Na+) there was no change in the urinary excretion of dopamine and noradrenaline (In their free or conjugated forms). There was, however, a marked surge 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 effect on the surge in excretion of urinary conjugated dopamine. Saline infusion decreased proximal fractional Na+ reabsorption. Administration of carbidopa delayed but did not prevent this decrease. The effects of saline infusion and of carbidopa on the urinary excretion of dopamine and noradrenaline from hypertensive patients were similar to those observed with the healthy volunteers.
  
  
  CONCLUSIONS
  These findings indicate that volume expansion by intravenous saline infusion has no appreciable effect on the urinary free dopamine excretion from normal or hypertensive humans; with any apparent increase, it is important to exclude the possibility of conversion of conjugates to free dopamine in vitro. Furthermore, that carbidopa administration did not inhibit the afternoon surge of conjugated dopamine suggests that administration of carbidopa is deficient as a tool to investigate the functional role of the renal dopamine system.
authors.affiliation: Department of Clinical Pharmacology, Royal North Shore Hospital, St. Leonards, NSW, Australia.
authors.forename: G S
authors.initials: GS
authors.lastname: Stokes
authors.forename: J C
authors.initials: JC
authors.lastname: Monaghan
authors.forename: D N
authors.initials: DN
authors.lastname: Pillai
mesh_terms: D000293:Adolescent; D000328:Adult; D000450:Aldosterone / Q000097:blood; D065105:Aromatic Amino Acid Decarboxylase Inhibitors; D009320:Atrial Natriuretic Factor / Q000097:blood; D002230:Carbidopa / Q000494:pharmacology*; D004298:Dopamine / Q000652:urine*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000652:urine*; D007262:Infusions, Intravenous; D007552:Isotonic Solutions; D008297:Male; D008875:Middle Aged; D009318:Natriuresis / Q000187:drug effects; D009638:Norepinephrine / Q000652:urine; D012083:Renin / Q000097:blood; D012709:Serum Albumin / Q000378:metabolism; D012965:Sodium Chloride / Q000008:administration & dosage*
chemical_list: D065105:Aromatic Amino Acid Decarboxylase Inhibitors; D004791:Enzyme Inhibitors; D007552:Isotonic Solutions; D012709:Serum Albumin; D012965:Sodium Chloride; D000450:Aldosterone; D009320:Atrial Natriuretic Factor; D012083:Renin; D002230:Carbidopa; D004298:Dopamine; D009638:Norepinephrine