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 kaliure sis might be explained by a felodipine-induced inhibition of aldostero ne release. The natriuresis with calcium entry blockers could not be a ttributed to a similar mechanism but might be due to the stimulation o f intrarenal natriuretic systems such as the dopaminergic system. We s tudied whether the aselective dopamine antagonist metoclopramide preve nts the natriuresis with low and therapeutic felodipine doses and whet her metoclopramide-induced aldosterone release promotes kaliuresis wit h felodipine. Twelve healthy male volunteers participated in a randomi zed, placebo-controlled, crossover study comparing felodipine infusion during metoclopramide with felodipine alone. Metoclopramide had no si gnificant influence on the pronounced and dose-dependent increases of renal plasma flow and urinary sodium excretion with felodipine. Metocl opramide increased plasma aldosterone concentration from 0.17+/-0.03 t o 0.60+/-0.14 nmol/L, and subsequent felodipine infusion clearly incre ased urinary potassium excretion by 23+/-6 and 35+/-8 mu mol/min (low and therapeutic doses, respectively). In contrast, potassium excretion remained stable with felodipine alone (+5+/-4 and +7+/-5 mu mol/min, respectively). In conclusion, the natriuretic action of calcium entry blockers cannot be blocked by the aselective dopamine antagonist metoc lopramide. This natriuresis is accompanied by kaliuresis only in the p resence of elevated endogenous aldosterone concentrations. The ability of calcium entry blockers to prevent a rise of plasma aldosterone thu s seems essential for the prevention of urinary potassium losses.