Andries Smit

Renal and Endocrine Effects of Fenoldopam and Metoclopramide in Normal Man

The effects of fenoldopam (FD), a selective dopamine-1 (DA1) agonist in doses from 0.05 to 0.50 micrograms/kg/min and of the aselective dopamine antagonist metoclopramide (MCP) on blood pressure (BP), sodium excretion and renal hemodynamics were investigated in 10 healthy volunteers. During FD infusion the diastolic BP fell 9 mm Hg with a rise in heart rate. During combined infusion of FD and MCP no changes in BP occurred. Effective renal plasma flow rose for all doses of FD with a maximal increase of 36% and was not influenced by MCP infusion. Glomerular filtration rate remained unchanged. FD induced an increase in sodium and calcium excretion compared to placebo study, which was abolished by MCP. A marked rise of plasma renin activity during FD infusion was noted, blunted by MCP. MCP induced a marked increase of aldosterone, sustained, but blunted, during subsequent FD infusion, suggesting a DA1-mediated influence on aldosterone secretion. During infusion of FD alone, an increased urinary dopamine excretion was observed. We conclude that FD induces: (1) systemic and renal vasodilation and (2) natriuresis by direct stimulation of DA1 receptors in the proximal tubule, which is (partially) counteracted by a rise of plasma renin activity and subsequently of aldosterone.

IMPAIRED RENAL HEMODYNAMIC BUT CONSERVED NATRIURETIC RESPONSE TO DOPAMINE IN PATIENTS WITH RENAL-DISEASE

Renal hemodynamics and sodium excretion were determined before and during infusion of dopamine in doses ranging from 0.25 to 8 micrograms/kg/min in healthy volunteers (n = 15) and in patients with renal disease and moderately impaired renal function (n = 21, baseline glomerular filtration rate 34-85 ml/min). While in normal volunteers dopamine resulted in marked renal vasodilation (maximal fall in filtration fraction 24%), in patients with moderately impaired renal function, the renal vasodilatory response to dopamine was impaired (maximal fall in FF 13%) and was found to depend on baseline glomerular filtration rate. Infusion of dopamine in doses of 2 micrograms/kg/min and higher resulted in an increase in urinary sodium excretion, which was comparable for healthy volunteers and patients with renal disease. We conclude that dopamine results in a predominantly efferent glomerular vasodilation and, therefore, may be salutary in lowering intraglomerular hypertension. However, in patients with renal disease the renal hemodynamic response to dopamine infusion is impaired compared to healthy volunteers, while the natriuretic response is maintained.

THE EFFECTS OF ALPHA-ADRENOCEPTOR BLOCKADE ON DOPAMINE-INDUCED RENAL VASODILATION AND NATRIURESIS

SummaryTo establish the effects of alpha-adrenoceptor blockade on dopamine-induced changes in renal hemodynamics and sodium excretion, dopamine dose-response curves were performed without and with pretreatment with the selective postsynaptic alpha1-adrenoceptor antagonist prazosin in normal volunteers and in patients with renal disease and moderately impaired renal function.Prazosin (1 mg p. o. every 4 h) in 7 volunteers did not significantly affect baseline values but impaired the response of effective renal plasma flow (ERPF) and filtration fraction (FF) to infusions of dopamine in doses ranging from 0.5 to 8 μg/kg per minute and completely abolished the dopamine-induced increase in sodium excretion. In 7 patients with renal disease and a glomerular filtration rate (GFR) ranging from 38–85 ml/min pretreatment with prazosin did not affect baseline ERPF, GFR or FF or their response to dopamine infusion, but sodium excretion and its response to dopamine infusion were reduced (fractional excretion of sodium at baseline 1.78 without and 0.89 with prazosin pretreatment).We conclude that alpha1-adrenoceptor blockade with prazosin abolishes the effects of exogenous dopamine on sodium excretion in normal man. Prazosin also impairs the renal vasodilatory action of dopamine. However, the effect on sodium excretion is not directly related to inhibition of dopamine-induced renal vasodilation since in patients with renal disease prazosin also markedly reduces sodium excretion but does not influence the renal hemodynamic effects of dopamine.