Renal and neurohumoral effects of ibopamine and metoclopramide in normal man.

Abstract

The effects of 100 mg ibopamine, an orally active nonselective dopamine agonist on renal haemodynamics, sodium excretion, blood pressure (BP), heart rate (HR) and neurohumoral parameters were investigated in 10 healthy volunteers, with and without metoclopramide pretreatment. A small and temporary rise of glomerular filtration rate (GFR) was found after ibopamine without but not with metoclopramide pretreatment. No differences in effective renal plasma flow (ERPF) but a small rise in sodium excretion were observed comparing ibopamine with control. Metoclopramide induced a fall in sodium excretion which was not reversed by ibopamine. Ibopamine failed to affect BP and HR and no changes of PRA or plasma aldosterone concentration (PAC) were found. Metoclopramide induced a pronounced increase of PAC which was blunted by ibopamine. Plasma and urinary catecholamines were unchanged for all study days. We conclude that ibopamine induces natriuresis probably not by the observed small and temporary renal haemodynamic effects but by direct stimulation of DA1 dopamine receptors in the proximal tubule.

Ibopamine

“…In healthy volunteers and patients with severe congestive heart failure, single doses of ibopamine 50 to 200mg significantly reduced plasma aldosterone levels (Incerti et al 1986;Rolandi et al 1986) or had no significant effect on this parameter (Girbes et al 1991;Nakano et al 1986), and either decreased plasma renin activity (by 30 to 35%) [Nakano et al 1986;Wehling et al 1990] or had no significant effect (Girbes et al 1991(Girbes et al , 1993Incerti et al 1986). There was no significant alteration in plasma aldosterone levels or plasma renin activity after ibopamine 100mg 3 times daily for 4 weeks (Morimoto et al 1989), whereas Pizzorni et al (1991) demonstrated a significant decrease in aldosterone levels after administration of ibopamine 100mg 3 times daily for 12 weeks, but a similar decrease was also observed after placebo.…”

Other agents

“…8,13 It also directly reduces activation of the renin-angiotensin system and inhibits aldosterone secretion. [14][15][16] Three prospective, non-controlled, small studies by single centres [3][4][5] have reported a significant improvement in renal function indices (plasma creatinine, reciprocal plasma creatinine or creatinine clearance) in patients with mild-tomoderate CKD treated with ibopamine 100 mg daily for periods ranging from 6 to 24 months.…”

“…The latter point may be particularly relevant since ibopamine has been shown to exert an antagonistic effect against angiotensin II at both a glomerular and tubular level 8,13 . It also directly reduces activation of the renin‐angiotensin system and inhibits aldosterone secretion 14–16 …”