Metoclopramide stimulates kaliuresis during felodipine without affecting its natriuresis.
Calcium entry blockers such as felodipine induce natriuresis without a parallel rise of potassium excretion. Previous studies with exogenous aldosterone and felodipine have suggested that the absence of kaliuresis might be explained by a felodipine-induced inhibition of aldosterone release. The natriuresis with calcium entry blockers could not be attributed to a similar mechanism but might be due to the stimulation of intrarenal natriuretic systems such as the dopaminergic system. We studied whether the aselective dopamine antagonist metoclopramide prevents the natriuresis with low and therapeutic felodipine doses and whether metoclopramide-induced aldosterone release promotes kaliuresis with felodipine. Twelve healthy male volunteers participated in a randomized, placebo-controlled, crossover study comparing felodipine infusion during metoclopramide with felodipine alone. Metoclopramide had no significant influence on the pronounced and dose-dependent increases of renal plasma flow and urinary sodium excretion with felodipine. Metoclopramide increased plasma aldosterone concentration from 0.17 +/- 0.03 to 0.60 +/- 0.14 nmol/L, and subsequent felodipine infusion clearly increased urinary potassium excretion by 23 +/- 6 and 35 +/- 8 mumol/min (low and therapeutic doses, respectively). In contrast, potassium excretion remained stable with felodipine alone (+5 +/- 4 and +7 +/- 5 mumol/min, respectively). In conclusion, the natriuretic action of calcium entry blockers cannot be blocked by the aselective dopamine antagonist metoclopramide. This natriuresis is accompanied by kaliuresis only in the presence of elevated endogenous aldosterone concentrations. The ability of calcium entry blockers to prevent a rise of plasma aldosterone thus seems essential for the prevention of urinary potassium losses.
Department of Medicine, Sint Radboud Hospital, University of Nijmegen, Netherlands.
H W
HW
van Hamersvelt
J F
JF
Wetzels
R A
RA
Koene
F T
FT
Huysmans
D000328:Adult; D000450:Aldosterone / Q000097:blood; D000704:Analysis of Variance; D001794:Blood Pressure / Q000187:drug effects; D002712:Chlorides / Q000652:urine; D018592:Cross-Over Studies; D015736:Felodipine / Q000494:pharmacology*; D005919:Glomerular Filtration Rate / Q000187:drug effects*; D006801:Humans; D007668:Kidney / Q000098:blood supply / Q000187:drug effects / Q000502:physiology*; D008094:Lithium / Q000652:urine; D008297:Male; D008787:Metoclopramide / Q000494:pharmacology*; D009318:Natriuresis / Q000187:drug effects*; D010919:Placebos; D011188:Potassium / Q000652:urine*; D012039:Regional Blood Flow / Q000187:drug effects; D012079:Renal Circulation / Q000187:drug effects*; D012964:Sodium / Q000652:urine; D013997:Time Factors
D002712:Chlorides; D010919:Placebos; D000450:Aldosterone; D008094:Lithium; D012964:Sodium; D008787:Metoclopramide; D015736:Felodipine; D011188:Potassium