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)
Smit
A J
AJ
Department of Medicine, State University Hospital Groningen, The Netherlands.
Meijer
S
S
Wesseling
H
H
Donker
A J
AJ
Reitsma
W D
WD
D000328:Adult; D000450:Aldosterone / Q000097:blood; D001794:Blood Pressure / Q000187:drug effects; D018492:Dopamine Antagonists; D004305:Dose-Response Relationship, Drug; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006801:Humans; D007668:Kidney / Q000098:blood supply / Q000187:drug effects*; D007674:Kidney Diseases / Q000503:physiopathology*; D008297:Male; D008787:Metoclopramide / Q000494:pharmacology*; D008875:Middle Aged; D012039:Regional Blood Flow / Q000187:drug effects; D012083:Renin / Q000097:blood; D012964:Sodium / Q000652:urine; D014563:Urodynamics; D001613:beta 2-Microglobulin / Q000652:urine; D005723:gamma-Glutamyltransferase / Q000652:urine
D018492:Dopamine Antagonists; D001613:beta 2-Microglobulin; D000450:Aldosterone; D012964:Sodium; D005723:gamma-Glutamyltransferase; D012083:Renin; D008787:Metoclopramide