Comparison of the effects on urinary sodium excretion of indomethacin and of carbidopa in normal volunteers given an intravenous saline infusion.
1. Dopamine and prostaglandins are putative endogenous natriuretic hormones. The role of each in facilitating natriuresis induced by intravenous saline infusion was examined in normal volunteers in relation to administration of carbidopa, a dopadecarboxylase inhibitor, and indomethacin, an inhibitor of prostaglandin synthetase. 2. In a placebo-controlled, randomized study, 13 subjects received carbidopa (100 mg) and 12 received indomethacin (50 mg). Proximal and distal renal tubular Na+ reabsorption were determined using exogenous lithium clearance. 3. On the control day, 2 litres of 0.9% saline (308 mmol Na+) given intravenously in 3 h, resulted in volume expansion and natriuresis. Carbidopa reduced the urinary dopamine/noradrenaline ratio but showed no anti-natriuretic effect and no effect on fractional Na+ reabsorption. Indomethacin diminished natriuresis and increased distal fractional Na+ reabsorption in proportion to the antinatriuretic effect. 4. The changes in plasma concentrations of albumin, aldosterone, atrial natriuretic peptide and renin activity associated with volume expansion were not modified by either carbidopa or indomethacin. Urinary prostaglandin E2 excretion was decreased transiently by indomethacin and was unaffected by carbidopa. 5. This study suggests that prostaglandins may modulate urinary Na+ excretion during saline-induced natriuresis through inhibition of distal tubular Na+ reabsorption. No role for free dopamine as a modulator of renal Na+ handling could be assigned on the basis of the findings with carbidopa.
Stokes
G S
GS
Department of Clinical Pharmacology, Royal North Shore Hospital, St Leonards, New South Wales, Australia.
Monaghan
J C
JC
Pillai
D N
DN
D000328:Adult; D009320:Atrial Natriuretic Factor / Q000097:blood; D002230:Carbidopa / Q000494:pharmacology*; D015232:Dinoprostone / Q000652:urine; D018492:Dopamine Antagonists / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology*; D007262:Infusions, Intravenous; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D008094:Lithium / Q000493:pharmacokinetics; D008297:Male; D011448:Prostaglandin Antagonists / Q000494:pharmacology*; D012964:Sodium / Q000008:administration & dosage / Q000378:metabolism / Q000652:urine*
D018492:Dopamine Antagonists; D011448:Prostaglandin Antagonists; D009320:Atrial Natriuretic Factor; D008094:Lithium; D012964:Sodium; D015232:Dinoprostone; D002230:Carbidopa; D007213:Indomethacin