Abstract: Background: Furosemide, a commonly used diuretic, activates the circulating renin-angiotensin-aldosterone system (RAAS) in other species. Little is known about RAAS activation in horses.
Hypothesis/Objectives: We hypothesize that furosemide will cause transient elevation in both classical and alternative RAAS hormones.
Animals: Adult thoroughbreds from a university teaching herd were used for the cross over study design (n=6) and baseline hormone levels (n=8).
Methods: Horses received either intravenous furosemide (1 mg/kg) or saline. Circulating RAAS hormones were quantified at 0, 0.25, 0.5, 4, and 24 hours post administration, via liquid chromatography-tandem mass spectrometry and/or equilibrium dialysis. Values were compared with a repeated measures mixed model. Paired protease inhibited samples were also analyzed and compared with Spearman’s Correlation. Data are presented as median (baseline) or difference in mean (elevation), [95% CI].
Results: Only Angiotensin-II (7.4 [4.8-10.7] pMol/L) was consistently above the limit of quantification at baseline. Furosemide resulted in an increase in Angiotensin I (8.0 [1.04-15.03] pMol/L, P=.02), Angiotensin-II (33.7 [10.0-57.4] pMol/L, P=.002), Angiotensin-IV (2.0 [.64-3.39] pMol/L, P=.001), Angiotensin 1-5 (5.6 [1.84-9.32] pMol/L, P=.0009) and Aldosterone (180.8 [3.1-358.5] P=.04) compared to saline at four hours. Correlation between protease inhibition and equilibrium dialysis was high for Angiotensin-I and Angiotensin II (r = 0.81 and 0.86, respectively; P< 0.0001).
Conclusions and clinical importance: Baseline levels of circulating RAAS hormones are low in healthy horses. Furosemide produced an increase in hormones associated with both the classical and alternative RAAS pathways. Comprehensive RAAS data offers a model to study pharmacologic and pathologic activation in horses.
