Central dopaminergic regulation of aldosterone secretion in sheep.

Abstract

SUMMARY Central dopaminergic mechanisms involved in the regulation of plasma aldosterone concentration were investigated in 16 conscious sheep following Na depletion with intramuscularly administered furosemide. Intracerebroventricular infusion of dopamine (20 /xg/min) decreased plasma aldosterone significantly to 52 ± 8% of basal level and increased plasma renin activity (PRA) significantly to 172 ± 25% of basal level in this animal model. In addition, intracerebroventricular infusion of the dopamine antagonist metoclopramide (20 /ug/min) in artificial cerebrospinal fluid vehicle significantly increased aldosterone levels to 144 ±14% of basal level and decreased PRA to 62 ± 5% of basal value. Neither intracerebroventricular infusion of the vehicle nor intravenous infusions of metoclopramide or dopamine at the same doses changed aldosterone or PRA levels. Intracerebroventricular bolus injections of metoclopramide (20 /xg/kg in 0.4 ml of vehicle) were also effective, increasing aldosterone levels to 266 ± 22% of basal level and decreasing PRA to 70 ± 12% of basal level. Intravenous bolus injections of the same dose of metoclopramide were ineffective. Dopamine was infused intracerebroventricularly into two uniadrenalectomized sheep with the remaining adrenal transplanted to the neck. Aldosterone levels were decreased to 49 ± 10% of basal level, and PRA was increased to 157 ±10% of basal value. None of the infusions or injections changed arterial or intracranial pressure, or plasma K, Na, and cortisol levels. These data indicate that endogenous or exogenous dopamine may act on central dopamine receptors to decrease plasma aldosterone concentration by an unknown humoral mechanism. The known aldosterone regulators, plasma Na, K, angiotensin II, and adrenocorticotropic hormone, are not involved in the regulation. (Hypertension 10: 157-163, 1987) KEY WORDS • brain dopaminergic pathway transplant • metoclopramide aldosterone secretion adrenal I N earlier studies, 1 we showed that centrally administered dopamine inhibited the release of aldosterone, an effect that is independent of changes in plasma Na, K, adrenocorticotropic hormone (ACTH), and angiotensin II (ANG II) levels. However, these studies did not clarify whether the effects of centrally infused dopamine were due to central or to peripheral actions or the mechanism by which central dopamine might suppress aldosterone secreFrom the

Dopamine is taken up from the circulation by, and released from, local noradrenergic varicose axon terminals in zona glomerulosa of the rat: a neurochemical and immunocytochemical study

“…It is unlikely, however, that these cells would be able to store and release DA in amounts large enough to affect glomerulosa cell function, and certainly not in response to neuronal activity. Intracerebroventricular administration of DA was shown to decrease aldosterone plasma levels (Bell & Gillespie, 1981;Huang et al 1987). The results obtained with drugs in clinical practice (Van Loon & Sole, 1980) and in animal experiments are thus gener¬ ally equally difficult to interpret; namely, how meto¬ clopramide, a DA2-receptor antagonist, stimulates aldosterone secretion in both man and rat (Carey et al 1980;Brown et al 1982;Aguilera et al 1984).…”

“…The results obtained with drugs in clinical practice (Van Loon & Sole, 1980) and in animal experiments are thus gener¬ ally equally difficult to interpret; namely, how meto¬ clopramide, a DA2-receptor antagonist, stimulates aldosterone secretion in both man and rat (Carey et al 1980;Brown et al 1982;Aguilera et al 1984). For all of these reasons, a central mode of action of DA rather than local action in the adrenal cortex has also been suggested (McDougall et al 1981; Whitehouse et al 1982;Huang et al 1987). The problem still re¬ mains, however: where does DA come from to influ¬ ence aldosterone secretion at the level of the zona glomerulosa cell?…”