The aim of this study was to determine the effect of metoclopramide, a dopamine antagonist, on the secretion of aldosterone and other adrenocortical steroids in normal subjects. An i.v. bolus injection of 10 mg of metoclopramide significantly increased the plasma PRL, plasma aldosterone and 18-hydroxycorticosterone, but the plasma renin activity, plasma deoxycorticosterone, corticosterone and cortisol remained unchanged. The changes in plasma aldosterone induced by metoclopramide were significantly correlated with the basal levels of plasma aldosterone and renin activity. These results suggest that the response of plasma aldosterone to metoclopramide in normal subjects is influenced by the basal activity of renin-angiotensin-aldosterone system and the late step of aldosterone synthesis is stimulated by metoclopramide.

Captopril (SQ14,225), an orally administered angiotensin converting enzyme inhibitor, was given to 8 patients with idiopathic edema, in order to study the role of the renin-angiotensin-aldosterone system in orthostatic sodium and water retention. Compared to 5 normal subjects, patients with idiopathic edema showed significantly greater reduction in water and sodium excretion, and greater increment in plasma aldosterone and plasma renin activity, in the upright posture. Captopril significantly restored water and sodium excretion, attenuated the increment in plasma aldosterone, and enhanced the rise in plasma renin activity in patients with idiopathic edema. The effects of captopril on these variables were not remarkable in normal subjects. These results suggest that an enhanced response of the renin-angiotensin-aldosterone system to standing plays an important role in the pathophysiology of idiopathic edema.

This study was designed to investigate the effects of metoclopramide, a dopamine antagonist, on in vivo and in vitro aldosterone production in the rat. In addition, we examined the effect of various levels of sodium intake on the response of plasma aldosterone to metoclopramide. Metoclopramide (2\p=n-\50mg/kg) was given by ip injection to conscious rats. Metoclopramide induced a dose-related increase in plasma aldosterone, whereas it only increased plasma renin activity at high doses (20 and 50 mg/kg). The response of plasma aldosterone to 10 mg/kg of metoclopramide in the low-sodium group was greater than that in the high-sodium group. Metoclopramide had no effect on aldosterone production in isolated zona glomerulosa cells in vitro.

To investigate the mechanism of the central action of dopamine and its antagonist, metoclopramide, on the regulation of aldosterone, studies were performed in 54 conscious rats with and without bilateral nephrectomy.In normal and sham-operated rats, intracerebroventricular injection of dopamine resulted in a significant suppression of plasma renin activity and plasma aldosterone at 30min, and intracerebroventricular injection of metoclopramide resulted in a significant elevation of plasma renin activity and plasma aldosterone at 30 min without altering the plasma corticosterone and potassium levels. In bilaterally nephrectomized rats, the plasma renin activity was significantly reduced and it did not respond to dopamine or metoclopramide. In these rats, intracerebroventricular injection of metoclopramide exerted no effect on the plasma aldosterone, but intracerebroventricular injection of dopamine increased the plasma aldosterone slightly. However, this increase was not statistically significant.These findings suggest that the dopaminergic system in the brain is involved in the regulation of aldosterone secretion, mainly with changes in the peripheral reninangiotensin axis in rats.

The role of the renin-angiotensin system in polyuric patients was studied in 5 patients with pituitary diabetes insipidus, 1 patient with nephrogenic diabetes insipidus and 3 patients with psychogenic polydipsia by determining the plasma renin activity and infusing an angiotensin II analog, 1-Sar, 8-Ile angiotensin II. In all patients with diabetes insipidus, plasma renin activity was markedly increased and the blood pressure was reduced in 5 of 6 patients by the administration of the angiotensin II analog. In the other patient, the blood pressure remained unchanged. The plasma renin activity and response of blood pressure to the angiotensin II analog in a patient with nephrogenic diabetes insipidus were not significantly different from there of patients with pituitary diabetes insipidus. On the other hand, in all patients with psychogenic polydipsia, plasma renin activity was normal or low, and the blood pressure increased with the administration of the angiotensin II analog. These results suggest that evaluation of the renin-angiotensin system by determining plasma renin activity and infusing an angiotensin II analog is useful in differentiating between diabetes insipidus and psychogenic polydipsia.