Metoclopramide does not inhibit atrial natriuretic factor-stimulated diuresis in man

Abstract

Background: An understanding of the reflex hormonal responses that occur with a redistribution of the blood volume upon exposure to microgravity or during water immersion is operationally relevant. Further, dopamine receptor antagonists, which are used in the treatment of the motion sickness induced by microgravity, or at sea, may affect fluid metabolism. Atrial natriuretic factor (ANF) is a potent diuretic and natriuretic hormone that is released following central blood volume expansion in man. ANF is also a potent inhibitor of angiotensin- and potassium-stimulated aldosterone release.

Hypothesis: Since ANF-induced diuresis may be mediated by dopamine, we sought to determine whether inhibition of dopamine receptors blocks ANF-induced natriuresis and diuresis. Also, since ANF has been shown to inhibit aldosterone secretion induced by adrenocorticotropic hormone (ACTH) in vitro, we investigated whether ANF decreases aldosterone in man infused with exogenous ACTH.

Methods and results: In six healthy, sodium-replete men, infusion of synthetic ANF (0.01 microgram.kg.min, Anaritide, Wyeth Laboratories) significantly increased urine flow from 7.1 +/- 0.7 to 11.7 +/- 1.8 ml.min-1 (p < 0.05) and decreased aldosterone from 74.7 +/- 9.0 to 55.8 +/- 6.5 pg.ml-1 (p = N.S.). Metoclopramide (Met), a dopaminergic antagonist, increased plasma aldosterone from 104.5 +/- 8.9 to 163 +/- 12.5 pg.ml-1 (p < 0.05). ANF-induced diuresis was not inhibited by Met, but ANF significantly inhibited Met-stimulated increases in plasma aldosterone. ANF did not attenuate ACTH-stimulated increases in plasma aldosterone. Also, ANF-induced diuresis and natriuresis were not affected by concomitant infusions of ACTH, but the ANF-induced kaliuresis was significantly attenuated by ACTH.

Conclusion: These studies suggest: a) Synthetic ANF induces a diuresis, natriuresis and kaliuresis; b) the D2 receptor antagonist Met increases plasma aldosterone; c) ANF-induced diuresis is not subject to dopaminergic blockade with Met, but Met-induced increases in plasma aldosterone are inhibited by ANF; and d) ANF does not attenuate ACTH-stimulated increases in mineralocorticoid production. These studies have operational significance, as they demonstrate that D2 dopaminergic blockade by the antinausea agent metoclopramide does not prevent the effects of increased ANF in response to central volume expansion such as occurs during exposure to microgravity or following water immersion.