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.

Transport of Monoamine Transmitters by the Organic Cation Transporter Type 2, OCT2

“…But there is also evidence for OCT2h to exist in proximal tubule cells (7). There is ample evidence that renal dopamine is involved in the regulation of sodium excretion (27) and, surprisingly enough, in the anaesthetized rat, disprocynium24 does not only block dopamine excretion but acts as a high ceiling eukaliuric diuretic and natriuretic (28). The exact mechanism of this new pharmacological effect of disprocynium24 has not yet been clarified.…”

“…The exact mechanism of this new pharmacological effect of disprocynium24 has not yet been clarified. An indirect activation of dopamine D1 and D2 receptors, however, does not seem to be involved since pretreatment with the dopamine receptor blockers SCH23390 and S(Ϫ)-sulpiride fails to affect the diuretic action of disprocynium24 (28).…”

Eukaliuric natriuresis and diuresis in response to disprocynium24: studies on the tubular site of action

“…Recently, we reported that intravenous administration of the cyanine-related compound DP24 elicits a dose-dependent diuresis and natriuresis without significantly affecting potassium ion excretion (Mühlbauer et al 1997). These effects were observed in spite of a concomitant fall in arterial blood pressure.…”

“…Recently, we reported a new pharmacological feature of DP24: intravenous administration of DP24 elicited a dosedependent diuresis and natriuresis in spite of a fall in blood pressure (Mühlbauer et al 1997). Furthermore, this response to DP24 was accompanied by an effect uncommon to thiazides or loop diuretics, namely, DP24 did not affect renal potassium ion excretion.…”