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.

To evaluate the effect of administration of the labeled dosage of pimobendan to dogs with furosemide-induced activation of the renin-angiotensin-aldosterone system (RAAS). 12 healthy hound-type dogs. Dogs were allocated into 2 groups (6 dogs/group). One group received furosemide (2 mg/kg, PO, q 12 h) for 10 days (days 1 to 10). The second group received a combination of furosemide (2 mg/kg, PO, q 12 h) and pimobendan (0.25 mg/kg, PO, q 12 h) for 10 days (days 1 to 10). To determine the effect of the medications on the RAAS, 2 urine samples/d were obtained for determination of the urinary aldosterone-to-creatinine ratio (A:C) on days 0 (baseline), 5, and 10. Mean ± SD urinary A:C increased significantly after administration of furosemide (baseline, 0.37 ± 0.14 μg/g; day 5, 0.89 ± 0.23 μg/g) or the combination of furosemide and pimobendan (baseline, 0.36 ± 0.22 μg/g; day 5, 0.88 ± 0.55 μg/g). Mean urinary A:C on day 10 was 0.95 ± 0.63 μg/g for furosemide alone and 0.85 ± 0.21 μg/g for the combination of furosemide and pimobendan. 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.