Effect of dopaminergic blockade on plasma aldosterone in acquired hypoaldosteronism

The pathogenesis of acquired hypoaldosteronism, a frequent cause of hyperkalemia in patients with chronic renal failure, is poorly understood. The present studies were undertaken to investigate the role of dopamine in suppressing mineralocorticoid secretion in this syndrome. We studied the plasma aldosterone response to dopaminergic blockade with metoclopramide in 11 patients with chronic renal failure (5 of whom were hyperkalemic) and 7 normal controls. Following repetitive doses of metoclopramide, the normokalemic chronic renal failure patients showed an exaggerated aldosterone response (peak aldosterone 50 +/- 5 ng/dl or 1,385 +/- 138 pmol/l) compared to normal controls (24 +/- 4 ng/dl or 665 +/- 110 pmol/l). In the hyperkalemic chronic renal failure patients, however, metoclopramide failed to induce a significant increase in plasma aldosterone (peak aldosterone 13 +/- 3 ng/dl or 360 +/- 83 pmol/l). By contrast, metoclopramide stimulated prolactin secretion in both normokalemic and hyperkalemic chronic renal failure patients. The plasma renin activity and serum potassium values were unchanged in all 3 groups. Our data show that dopaminergic blockade with metoclopramide fails to stimulate aldosterone secretion in patients with acquired hypoaldosteronism. Thus this syndrome does not result from enhanced dopaminergic inhibition of aldosterone, but rather from an independent abnormality in aldosterone biosynthesis.