Metoclopramide stimulates kaliuresis during felodipine without affecting its natriuresis.

Abstract

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, placebocontrolled, 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 C alcium ehtry blockers (CEBs), especially dihydropyridines such as felodipine, are powerful vasodilating drugs useful for the treatment of hypertension.1 These drugs have short-term diuretic and natriuretic effects, 2 which may contribute to their antihypertensive action. Clearance studies in humans 3 "6 and some micropuncture studies in animals 79 have indicated that CEBs decrease proximal tubular sodium reabsorption. However, the mechanisms responsible for CEBmediated natriuresis remain unknown. Since selective administration of a CEB into the renal artery stimulates natriuresis, 10 an interaction with intrarenal natriuretic systems such as the dopaminergic system 11 could be involved.We and others have observed that the increased sodium excretion during calcium entry blockade is not accompanied by a parallel increase of potassium excretion. ,6,i2 This is rather surprising in view of the aforementioned CEB-mediated decrease of proximal tubular sodium reabsorption. We have previously demonstrated that simultaneous administration of exogenous aldosterone and felodipine was followed by a large increase of kaliuresis.13 Therefore, the attenuation of potassium excretion during calcium entry blockade might be explained by the well-known CEB-mediated inhibition of aldosterone release. © 1994 American Heart Association, Inc.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 /xmol/min (low and therapeutic doses, respectively). In contrast, potassium excretion remained stable with felodipine alone (+5±4 and +7±5 /xmol/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 pl...