Acute effect of pimobendan and furosemide on the circulating renin-angiotensin-aldosterone system in healthy dogs.
BACKGROUND
The renin-angiotensin-aldosterone system (RAAS) is activated in states of decreased cardiac output and by certain cardiovascular therapeutic agents, such as loop diuretics and vasodilators.


OBJECTIVE
Short-term treatment with the inodilator, pimobendan, will not activate the circulating RAAS because its vasodilatory action will be offset by its positive inotropic property, thereby ameliorating RAAS stimulation at the juxtaglomerular apparatus. Furthermore, pimobendan will suppress RAAS activation produced by furosemide.


METHODS
Nine healthy laboratory dogs were used in this study.


METHODS
Experimental, cross-over study. Dogs were administered pimobendan (0.5 mg/kg q12h) for 4 days followed by furosemide (2 mg/kg q12h) and then, after a wash-out period, a combination of the drugs. Aldosterone : creatinine (A : Cr) was measured at the end of each treatment cycle.


RESULTS
There was no significant increase in the average urinary A : Cr with the administration of pimobendan (control urinary A : Cr = 0.46, standard deviation (SD) 0.33; pimobendan A : Cr = 0.48, SD 0.28). There was a significant increase in the average urinary A : Cr after administration of furosemide (urinary A : Cr = 1.3, SD 0.70) and with the combination of furosemide and pimobendan (urinary A : Cr = 2.9, SD 1.6).


CONCLUSIONS
Short-term administration of high-dose pimobendan, does not activate the RAAS in healthy dogs. Pimobendan did not prevent RAAS activation associated with furosemide therapy. These results in healthy dogs suggest that furosemide therapy, with or without pimobendan, should be accompanied by RAAS suppressive therapy.
Sayer
M B
MB
College of Veterinary Medicine, North Carolina State University, Raleigh, NC, USA. pegbooth@yahoo.com
Atkins
C E
CE
Fujii
Y
Y
Adams
A K
AK
DeFrancesco
T C
TC
Keene
B W
BW
D000450:Aldosterone / Q000652:urine; D000818:Animals; D001806:Blood Urea Nitrogen; D002712:Chlorides / Q000097:blood; D018592:Cross-Over Studies; D004285:Dogs / Q000097:blood* / Q000652:urine; D005260:Female; D005665:Furosemide / Q000494:pharmacology*; D008297:Male; D010758:Phosphorus / Q000097:blood; D011188:Potassium / Q000097:blood; D011724:Pyridazines / Q000494:pharmacology*; D012084:Renin-Angiotensin System / Q000187:drug effects*; D012964:Sodium / Q000097:blood; D049994:Sodium Potassium Chloride Symporter Inhibitors / Q000494:pharmacology*; D014665:Vasodilator Agents / Q000494:pharmacology*
D002712:Chlorides; D011724:Pyridazines; D049994:Sodium Potassium Chloride Symporter Inhibitors; D014665:Vasodilator Agents; D010758:Phosphorus; C041648:pimobendan; D000450:Aldosterone; D005665:Furosemide; D012964:Sodium; D011188:Potassium