Is aldosterone secretion under dopaminergic control?

ALTHOUGH angiotensin, potassium, sodium, and adrenocorticotrophic hormone are generally acknowledged as major direct influences on aldoster-one secretion, there is a strong case for the existence of other factors which affect aldosterone secretion and which may play physiological roles (see Cogh-lan et al., 1979, for review). The plasma aldosterone response to metoclopramide (a dopamine antagonist) initially reported by Norbiato et al. (1977) is independent of known aldosterone-controlling factors and suggests the existence of a novel aldoster-one-regulating mechanism. The proposition that aldosterone production may be subject to dopami-nergic inhibition was originally suggested by Eld-wards et al. (1975) and received support from the in vitro studies of McKenna et al. postulated aldosterone secretion to be under maximal tonic dopaminergic inhibition in normal man. This postulate rests upon two observations—that, although metoclopramide causes plasma aldoster-one to rise 2-to 3-fold (Norbiato et al., neither dopamine nor bromocrip-tine (a dopamine agonist) modify basal plasma al-dosterone (Carey et aL, 1979, 1980; Noth et aL, 1980). The present review will survey recent studies of the effects on aldosterone of dopamine agonists and antagonists, including bromocriptine and metoclo-pramide, and of drugs modifying dopamine metabolism. The results of these studies will be related to the hypothesis of a physiological role for dopamine in aldosterone control. Finally, an assessment of the relative merits of the case for and against a role for dopamine in aldosterone control will be presented. Although an initial study reported metoclopram-ide, 5 mg, iv, to be without effect on plasma aldos-terone (Ogihara et al, 1977), all subsequent studies have shown an increase in plasma aldosterone in response to metoclopramide administration. An intravenous bolus of 10 mg metoclopramide produces a rapid 2-to 3-fold increase in plasma aldosterone, which reaches a peak between 2 and 10 minutes and returns to basal levels over the next 1-3 hours in both man (Norbiato et al. In contrast, oral me-toclopramide (10 mg) produced a rise in plasma aldosterone in only two of five subjects (Noth et al., 1980). The increase in plasma aldosterone is accompanied by a parallel increase in urinary excretion of the acid-labile conjugate of aldosterone (Carey et al., 1979). Since metoclopramide is without effect on aldosterone metabolic clearance rate (Brown et al., 1979a), the increases in plasma aldosterone produced by metoclopramide represent an increase in aldosterone production by the adrenal. The effect of metoclopramide upon aldosterone secretion appears to be independent of known al-dosterone-regulating mechanisms. The plasma al-dosterone response …