Selectivity of metoclopramide for endocrine versus renal effects of dopamine in normal humans

The purpose of the present study was to evaluate the effect on renal function of dopamine (low dose, 2 micrograms/kg/min) inhibition by a low-dose infusion of metoclopramide. Prolactin and aldosterone levels were measured to assess metoclopramide's endocrine effects. Six salt-loaded subjects were studied by standard renal clearance techniques during water diuresis. Dopamine infusion produced an increase in renal plasma flow, fractional excretion of sodium, osmolar and free water clearances, urine volume, and solute delivery out of the proximal tubule. Solute and fluid absorption decreased in the distal nephron. These effects were evident within the first hour and peaked during the third hour. Metoclopramide slightly attenuated the dopamine-induced increase in renal plasma flow; statistical significance was obtained only during the second hour. None of the other renal function changes were inhibited. Serum prolactin and aldosterone levels were significantly increased following metoclopramide. Dopamine infusion attenuated the rise in prolactin levels but did not significantly affect aldosterone levels. The variance between previous reports and the present one may be due to the use of water diuresis, salt-loading, or methodological factors. Metoclopramide infused at 0.1 mg/kg/h appears selective for DA2 receptors, and low-dose dopamine-induced changes in renal function are DA1 receptor-mediated.