Metoclopramideのアルドステロン分泌刺激機序, 特に原発性アルドスデロン症における検討

抄録

In order to clarify the role of dopamine in aldosterone secretion, the effect of metoclopramide, a dopamine antagonist, on plasma aldosterone concentration was evaluated in five normal subjects and five patients with primary aldosteronism, to whom 2mg/day of dexamethasone was administered for 2 days to eliminate the influence of ACTH prior to the study.
The dexamethasone treatment slightly decreased plasma aldosterone concentrations (PAC) from 14.2 ± 1.8 (mean ± s.e.) to 12.9 ± 2.3ng/dl in normal subjects and also from 36.9 ± 15.6 to 35.1 ± 16.7ng/dl in patients with primary aldosteronism. Plasma cortisol concentrations (PF) were markedly decreased by dexamethasone administration from 6.1 ± 2.1 to 1.1 ± 0.1μg/dl (p<0.001) in normal subjects and from 7.1 ± 1.8 to 0.7 ± 0.1 μg/dl (p < V0.001) in patients with primary aldosteronism, while plasma renin activity (PRA) and plasma prolactin concentrations (PRL) did not charge with the dexamethasone administration in either normal subjects or patients with primary aldosteronism.
An i.v. bolus injection of metoclopramide (10mg) rapidly increased PAC from 12.9 ± 2.3 to 17.3 ± 3.3ng/dl (p < 0.05) in normal subjects and from 35.1 ± 16.7 to 38.5 ± 17.0 ng/dl (p < 0.05) 5 min after the administration in patients with primary aldosteronism. PAC elevated maximally to 23.8 ± 3.4ng/dl (p < 0.02) in normal subjects and to 45.1 ± 16.7 ng/dl (p < 0.02) in patients with primary aldosteronism 30 min after the administration of metoclopramide. There were no significant differences in change of PAC in response to metoclopramide between normal subjects and patients with primary aldosteronism. PRL elevated significantly from 4.5 ± 1.1 to 102.0 ± 9.3ng/ml (p < 0.001) in normal subjects and also from 8.7 ± 3.9 to 108.4 ± 23.1ng/ml (p < 0.01) in patients with primary aldosteronism 30 min after the administration. PRA, PF, serum potassium and sodium concentrations did not significantly change with the metoclopramide administration in either normal subjects or patients with primary aldosteronism. There was no significant relationship between the increase in PAC and PRA and the increase in PAC and PRL with metoclopramide in either normal subjects or patients with primary aldosteronism.
These results suggest that metoclopramide acts directly upon the adrenal cortex to stimulate the secretion of aldosterone, and that aldosterone secretion may be suppressed by dopamine in primary aldosteronism as well as in normal subjects.