1. The effects of intravenous metoclopramide on baseline values and dopamine dose–response curves for renal haemodynamics and natriuresis were investigated in healthy volunteers and patients with renal disease.
2. Dopamine infusion alone, in doses ranging from 0.25 to 8 μg min−1 kg−1, resulted in a dose-dependent increase in effective renal plasma flow (ERPF) and glomerular filtration rate (GFR) with a fall in filtration fraction (FF) in eight hydrated healthy volunteers and, to a lesser degree, in 12 patients with renal disease. An increase in natriuresis (urinary excretion of sodium, UNa+V), fractional excretion of sodium (FENa+) and diuresis (urine flow rate, UV) was found in both groups for doses of 2 μg min−1 kg−1 and higher.
3. Metoclopramide infusion did not alter baseline values of GFR, ERPF or FF, but shifted the dopamine dose–response curve for ERPF and FF in the healthy volunteers. Metoclopramide induced a fall in UNa+V and FENa+ in both groups (fall in baseline FENa+ from 1.52 to 0.71 during metoclopramide in healthy volunteers and from 1.23 to 0.56 in patients; P < 0.01) and blunted the natriuretic response to subsequent dopamine infusion. The fall in UNa+V during metoclopramide infusion showed a strong correlation with baseline GFR (r = −0.944). In the patients, the response for the fractional excretions of β2-microglobulin and γ-glutamyltransferase was comparable with that of FENa+.
4. Dopamine infusion induced a fall, and metoclopramide led to rise, in plasma aldosterone concentration.
5. We conclude that metoclopramide acts as a dopamine antagonist at the renal level in man. Endogenous dopamine secretion does not seem to have a role in maintaining ERPF or GFR in hydrated healthy volunteers or in patients with renal disease, but is important for mediating natriuresis. Dopamine-induced changes in natriuresis were not found to depend on changes in renal haemodynamics.