METOCLOPRAMIDE DOES NOT INHIBIT ATRIAL NATRIURETIC FACTOR-STIMULATED DIURESIS IN MAN

Background: An understanding of the reflex hormonal responses that occ ur with a redistribution of the blood volume upon exposure to microgra vity or during water immersion is operationally relevant. Further, dop amine receptor antagonists, which are used in the treatment of the mot ion sickness induced by microgravity, or at sea, may affect fluid meta bolism. Atrial natriuretic factor (ANF) is a potent diuretic and natri uretic hormone that is released following central blood volume expansi on in man. ANF is also a potent inhibitor of angiotensin- and potassiu m-stimulated aldosterone release. Hypothesis: Since ANF-induced diures is may be mediated by dopamine, we sought to determine whether inhibit ion of dopamine receptors blocks ANF-induced natriuresis and diuresis. Also, since ANF has been shown to inhibit aldosterone secretion induc ed by adrenocorticotropic hormone (ACTH) in vitro, we investigated whe ther ANF decreases aldosterone in man infused with exogenous ACTH. Met hods and Results: In six healthy, sodium-replete men, infusion of synt hetic ANF (0.01 mu g . kg . min, Anaritide, Wyeth Laboratories) signif icantly 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 ant agonist, 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 M et, but ANF significantly inhibited Met-stimulated increases in plasma aldosterone. ANF did not attenuate ACTH-stimulated increases in plasm a aldosterone. Also, ANF-induced diuresis and natriuresis were not aff ected by concomitant infusions of ACTH, but the ANF-induced kaliuresis was significantly attenuated by ACTH. Conclusion: These studies sugge st: a) Synthetic ANF induces a diuresis, natriuresis and kaliuresis; b ) the D-2 receptor antagonist Met increases plasma aldosterone; c) ANF -induced diuresis is not subject to dopaminergic blockade with Met, bu t Met-induced increases in plasma aldosterone are inhibited by ANF; an d d) ANF does not attenuate ACTH-stimulated increases in mineralocorti coid production. These studies have operational significance, as they demonstrate that D-2 dopaminergic blockade by the antinausea agent met oclopramide does not prevent the effects of increased ANF in response to central volume expansion such as occurs during exposure to microgra vity or following water immersion.