Effect of furosemide on comprehensive renin‐angiotensin‐aldosterone system activity of Thoroughbred horses

Abstract

Abstract Background Furosemide, a commonly used diuretic, activates the renin‐angiotensin‐aldosterone system (RAAS) in other species. Little is known about RAAS peptide activation in horses. Hypothesis/Objectives To evaluate equilibrium analysis as a practical method for RAAS quantification in horses and describe the RAAS response to a single dose of furosemide. We hypothesize that furosemide would cause transient increase in RAAS peptides in horses. Animals 14 healthy adult thoroughbreds from a university teaching herd. Methods Horses received either furosemide (1 mg/kg IV) or saline IV in a crossover study design. Protease‐inhibited samples were compared with equilibrium analysis samples with Deming regression analysis. Renin‐angiotensin‐aldosterone system hormones were evaluated at 0, 0.25, 0.5, 4, and 24 hours postadministration, via equilibrium analysis. Values were compared with a mixed effects model. Results Correlation between protease inhibition and equilibrium analysis was high for angiotensin I peptide (AngI) and angiotensin II peptide (AngII) (r = .92 and .95, respectively). Baseline RAAS peptide concentrations were below the limit of detection except AngII (median, 7.5 [range, 3.5‐14.0] pmol/L). Furosemide administration resulted in an increase in AngI (8.0 [0.5‐15.5] pmol/L, P = .03), AngII (33.7 [9.6‐57.9] pmol/L, P = .0008), angiotensin III peptide (AngIII) (2.9 [0.9‐4.9] pmol/L, P = .0005), angiotensin IV peptide (AngIV) (2.0 [0.6‐3.4] pmol/L, P = .0005), and angiotensin 1‐5 peptide (Ang1‐5) (5.6 [1.2‐5.9] pmol/L, P = .003) at 4 hours. Differences are reported as difference in the mean (95% confidence interval [CI]). Conclusions and Clinical Importance Furosemide produced an increase in hormones associated with both the classical and alternative RAAS pathways. Serum equilibrium analysis is practical for RAAS analysis in horses.

Keywords

• alternative RAAS
• equine
• loop diuretic
• RAAS