C08 - The Effect of Spironolactone on the Renin-Angiotensin-Aldosterone System in Dogs

Abstract: Background – Spironolactone has been associated with reduced risk of cardiac morbidity and mortality in humans and dogs with congestive heart failure. There is little evidence on the effect of spironolactone on biomarkers of the classical and alternative arms of the renin-angiotensin-aldosterone system (RAAS) in dogs.

Hypothesis/Objectives – To characterize the effect of spironolactone on the RAAS in healthy dogs.

Animals – Ten healthy purpose-bred Beagles.

Methods – Study dogs were randomly allocated to two spironolactone dosing groups (2 mg/kg or 4 mg/kg PO q24hr for 7 days). Angiotensin peptides and aldosterone serum levels before and after treatment were quantified by LC-MS/MS. Wilcoxon sum rank tests were performed to compare study variables between treatments and baseline. P-values < 0.1 were considered statistically significant.

Results – Following spironolactone treatment, dogs showed significant increases in angiotensin I (AngI median 136; IQR 77 – 167), AngII (median 70; IQR 39 – 81), and Ang(1-5) (median 52; IQR 41 – 62) compared to baseline (AngI median 63; IQR 38 – 112; p=0.08; AngII median 32; IQR 23 – 52; p=0.09; Ang(1-5) median 24; IQR 17 – 40; p=0.08). Changes from baseline in angiotensin peptides did not differ between study groups for the dosing range investigated.


Conclusions and clinical importance – Spironolactone treatment increases the activity of the classical and alternative RAAS pathways in healthy dogs. A greater pharmacological response was not observed for the higher dosing group, suggesting that a 2 mg/kg q24hr oral dose of spironolactone already reaches a plateau activity on RAAS.