The effect of carbidopa and lithium on the systemic and renal response to acute intravenous saline loading in normal man.
To assess a possible role for endogenous renal dopamine in sodium excretion, the dopa decarboxylase inhibitor carbidopa was given during intravenous salt loading. In addition, the effect of lithium on tubular sodium handling was separately determined. Nine males were studied randomly on three occasions, receiving placebo, lithium carbonate (1000 mg, 11 h prior to study) or carbidopa (100 mg x 2). On each day a baseline period was followed by infusion of isotonic saline (20 ml/kg per hour) over 3 h, and 6 h recovery. With placebo, sodium excretion increased markedly to a peak in the hour after infusion (0.15 +/- 0.03 to 0.73 +/- 0.12 mmol/min, P less than 0.01). Urine dopamine excretion increased modestly (1.33 +/- 0.12 to 1.67 +/- 0.13 mmol/min, P less than 0.01). Carbidopa effectively blocked dopamine output during the study. However, the natriuretic response was comparable to values on placebo at all time points. Fractional lithium clearance, a proposed measure of proximal tubular fluid rejection, increased significantly during saline infusion. However, baseline sodium excretion was greater in the presence of lithium, and plasma renin activity (PRA) was significantly elevated. In addition, the peak natriuretic response was smaller and cumulative sodium excretion reduced by 40% (P less than 0.01) compared to placebo. This study provides no evidence for a facilitatory role for dopamine in the natriuretic response to intravenous salt loading. Lithium, at subtherapeutic levels, cannot be presumed to be an inert marker, and clearance data must be interpreted with caution.
Jeffrey
R F
RF
University Department of Clinical Pharmacology, Royal Infirmary, Edinburgh, UK.
MacDonald
T M
TM
Freestone
S
S
Lee
M R
MR
D000328:Adult; D009320:Atrial Natriuretic Factor / Q000097:blood; D002230:Carbidopa / Q000494:pharmacology*; D004298:Dopamine / Q000502:physiology; D006801:Humans; D007262:Infusions, Intravenous; D007668:Kidney / Q000187:drug effects / Q000502:physiology; D008094:Lithium / Q000494:pharmacology*; D008297:Male; D009318:Natriuresis / Q000187:drug effects*; D012083:Renin / Q000097:blood; D012965:Sodium Chloride / Q000008:administration & dosage
D012965:Sodium Chloride; D009320:Atrial Natriuretic Factor; D008094:Lithium; D012083:Renin; D002230:Carbidopa; D004298:Dopamine