Effect of metoclopramide on dopamine-induced changes in renal function in healthy controls and in patients with renal disease

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 micrograms 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 micrograms 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 less than 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 beta 2-microglobulin and gamma-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.(ABSTRACT TRUNCATED AT 250 WORDS)