Dopaminergic Regulation of Aldosterone Secretion in Primary Aldosteronism: A Clinical Study.

Abstract

To assess the role of dopaminergic inhibition of aldosterone secretion in primary aldosteronism (PA) we studied the effect of dopaminergic DA2 blockade and stimulation in a series of consecutive cases of PA, and of primary hypertension (PH) as controls. Thirteen patients with confirmed PA (11 adenoma, 2 idiopathic hyperaldosteronism) and 8 primary hypertensive subjects (PH) were studied while on a 100 mmol/day sodium diet. Patients with aldosterone-producing adenoma were studied before, 1-2 wk after, and 6 months after surgery. The DA2-antagonist metoclopramide (10 mg i.v.) and the DA2-agonist dihydroergotoxine (6 ,ug/Kg b.w. i.v.) were administered on different days. The effect of the latter on adrenal vein aldosterone and cortisol levels was also studied in selected cases. Plasma aldosterone, prolactin, cortisol, renin activity, free catecholamines, ACTH, Na+ , K+ , heart rate, and blood pressure were measured before and repeatedly after administration of each drug. In both groups, metoclopramide significantly increased aldosterone, prolactin, and cortisol (p < 0.01), slightly decreased K+ , and did not change the other variables. In PA patients, the aldosterone output was significantly (p < 0.05) greater than in PH, and fell after surgery. There was no difference, however, in responsiveness to metoclopramide between PA and control patients. Dihydroergotoxine significantly decreased plasma prolactin and aldosterone levels and adrenal vein aldosterone in patients with PH. In contrast, despite a similar decrease in prolactin, in PA a significant (p < 0.05) increase in aldosterone was seen, both peripherally and in adrenal vein blood. Thus, in PA: 1) the response to DA2 blockade is qualitatively normal but quantitatively enhanced; 2) this enhancement disappears after removal of the adenoma and thus appears related to increased aldosterone-secreting tissue rather than to enhanced responsiveness; 3) the response stimulation by dihydroergotoxine is paradoxical in PA, and may be mediated through ACTH stimulation. (Hypertens Res 1994; 17: 105-115)

Subtyping of primary aldosteronism by adrenal vein sampling: effect of acute D2 receptor dopaminergic blockade on adrenal vein cortisol and chromogranin A levels

“…It is noteworthy that this study by showing that metoclopramide increased the plasma adrenal vein level of aldosterone demonstrates that this hormone is under tonic dopaminergic D 2 receptormediated inhibition and confirms previous limited observations (7). Whether this could improve the lateralization of excessive aldosterone to the affected side, and thereby the diagnosis of the surgically curable subtypes of PA, is currently being pursued in a large prospective study.…”

“…Dopamine is held to tonically inhibit aldosterone secretion because the selective D 2 receptor antagonist metoclopramide induces aldosterone release in humans (6,7). More recent evidence showed that the dopamine acts by blunting Ca 2C influx and protein kinase C phosphorylation (8), which suggests that its inhibitory effect involves the early steps of the steroidogenesis and therefore are not confined to aldosterone synthesis, but may involve also cortisol and its precursors.…”

New concepts in adrenal vein sampling for aldosterone in the diagnosis of primary aldosteronism

“…Several stimuli, including the 4-hour upright posture test, volume expansion procedures, infusion of angiotensin (Ang) II and corticotropin (ACTH), and administration of captopril, losartan, and dopaminergic (dopamine, DA 2 ) receptor agonists and antagonists [16] have, therefore, been exploited to functionally differentiate cases that can be cured by adrenalectomy from cases that cannot [17]. However, results of these procedures have been disappointing in differentiating between APA and IHA.…”