DISPROCYNIUM24 INDUCES A DOPAMINE-INDEPENDENT EUKALIURIC DIURESIS ANDNATRIURESIS IN THE ANESTHETIZED RAT

In the anaesthetized rat, intravenous administration of the isocyanine 1,1'-diisopropyl-2,4'-cyanine (disprocynium24) ar doses up to 600 mu g/kg resulted in marked diuresis and natriuresis without affecting uri nary potassium excretion, Fractional sodium excretion was increased ov er 10-fold indicating a high ceiling-diuretic action. The effects of d isprocynium24 on renal function were accompanied by a dose-dependent r eduction in heart rate (HR) and mean arterial blood pressure (MAP), Ac ute administration of 600 mu g/kg disprocynium24 decreased MAP by 25% and, in addition, caused a fall in glomerular filtration rate (GFR). S ince i) disprocynium24 has been shown to interfere with urinary dopami ne excretion (UDAV) and ii) dopamine has been implicated with the regu lation of renal sodium excretion, we hypothesized that the effects of disprocynium24 might be mediated by its effects on renal dopamine hand ling. The following findings, however, argue against this hypothesis. First, administration of disprocynium24 in single doses up to 600 mu g /kg caused a diuresis and natriuresis, but did not significantly affec t UDAV. Second, neither the systemic nor the renal response to disproc ynium24 were markedly altered by pretreatment with the dopamine D-1- o r D-2-receptor blockers SCH23390 (10 mu g.kg(-1).min(-1)) or S(-)sulpi ride (15 mu g.kg(-1).min(-1)), respectively.