Disprocynium24 induces a dopamine-independent, eukaliuric diuresis and natriuresis in the anaesthetized rat

Abstract

In the anaesthetized rat, intravenous administration of the isocyanine 1,1'-diisopropyl-2,4'-cyanine (disprocynium24) at doses up to 600 microg/kg resulted in marked diuresis and natriuresis without affecting urinary potassium excretion. Fractional sodium excretion was increased over 10-fold indicating a high ceiling-diuretic action. The effects of disprocynium24 on renal function were accompanied by a dose-dependent reduction in heart rate (HR) and mean arterial blood pressure (MAP). Acute administration of 600 microg/kg disprocynium24 decreased MAP by 25% and, in addition, caused a fall in glomerular filtration rate (GFR). Since i) disprocynium24 has been shown to interfere with urinary dopamine excretion (UDAV) and ii) dopamine has been implicated with the regulation of renal sodium excretion, we hypothesized that the effects of disprocynium24 might be mediated by its effects on renal dopamine handling. The following findings, however, argue against this hypothesis. First, administration of disprocynium24 in single doses up to 600 microg/kg caused a diuresis and natriuresis, but did not significantly affect U(DA)V. Second, neither the systemic nor the renal response to disprocynium24 were markedly altered by pretreatment with the dopamine D1- or D2-receptor blockers SCH23390 (10 microg x kg(-1) x min[-1]) or S(-)sulpiride (15 microg x kg(-1) x min[-1]), respectively.