Effects of furosemide and the combination of furosemide and the labeled dosage of pimobendan on the circulating renin-angiotensin-aldosterone system in clinically normal dogs

Abstract

Furosemide-induced RAAS activation appeared to plateau by day 5. Administration of pimobendan at a standard dosage did not enhance or suppress furosemide-induced RAAS activation. These results in clinically normal dogs suggested that furosemide, administered with or without pimobendan, should be accompanied by RAAS-suppressive treatment.

Effect of furosemide and high-dosage pimobendan administration on the renin-angiotensin-aldosterone system in dogs

“…Results of previous studies 11,20 in the authors' laboratory and those of the present study suggest that, at the recommended dosage, pimobendan does not potentiate furosemide-induced RAAS activation, and at high dosages, it causes a mild, early, and transient increase in RAAS activation in clinically normal dogs receiving furosemide.…”

“…35 The development of metabolic alkalosis during furosemide-induced activation of the RAAS has been detected in clinical cases and in a previous study. 11 The increase in HR seen in group F + P was compatible with a positive chronotropic effect of pimobendan. This may also have been caused by a baroreceptormediated reflex in response to diuretic administration and resultant volume contraction, possibly potentiated by pimobendan.…”

“…This inotropic effect does not, however, lead to suppression of the furosemide-induced RAAS in healthy dogs. 11 Another possible explanation is that the positive inotropic effect of pimobendan may lag behind the vasodilatory effect, allowing the PDE III-induced vasodilatory effect to predominate early (during the first few days after administration), with reversal when either pimobendan' s inhibition of PDE III and resultant vasodilation plateaus or the drug' s positive inotropic effect catches up, to offset the vasodilatory effect on renal blood flow with its resultant renin release.…”

“…At a high dosage (0.5 mg/kg, PO, q 12 h), pimobendan potentiated furosemide-induced activation of the RAAS in the short-term (3 days), 19 but this did not occur when the recommended dosage (0.25 mg/kg, PO, q 12 h) was administered for 10 days. 11 Renin-angiotensin-aldosterone system forward from those studies was the evaluation of the effect of high-dosage pimobendan (0.6 mg/kg, PO, q 12 h) on the furosemide-activated RAAS of healthy dogs over a longer time period (10 days), to confirm or refute our earlier findings. 19 20 The use of such dosages illustrates the clinical importance of determining whether high-dosage pimobendan potentiates the effect of furosemide on the RAAS.…”

“…11,19 In those studies, as with the present study, furosemide (as an RAAS stimulant) was administered at a dosage of 2 mg/kg, PO, every 12 hours. At a high dosage (0.5 mg/kg, PO, q 12 h), pimobendan potentiated furosemide-induced activation of the RAAS in the short-term (3 days), 19 but this did not occur when the recommended dosage (0.25 mg/kg, PO, q 12 h) was administered for 10 days.…”