Effect of furosemide on comprehensive renin-angiotensin-aldosterone system activity of Thoroughbred horses.
Authors: Lehman Mallory L, Domenig Oliver, Ames Marisa K, Morgan Jessica M
Journal: Journal of veterinary internal medicine
Summary
# Editorial Summary Furosemide's activation of the renin-angiotensin-aldosterone system (RAAS) is well-documented in other species, yet this compensatory response has remained poorly characterised in horses despite the drug's widespread use in equine practice. Mallory and colleagues administered either furosemide (1 mg/kg IV) or saline to 14 healthy Thoroughbreds in a crossover design, measuring multiple RAAS peptides at five timepoints over 24 hours using serum equilibrium analysis—a method they validated against traditional protease-inhibited sampling (correlation coefficients of 0.92–0.95). Furosemide triggered a substantial four-hour surge across the RAAS cascade: angiotensin II increased from baseline 7.5 to 33.7 pmol/L, with statistically significant elevations also observed in angiotensin I, III, IV and angiotensin 1-5, confirming activation of both classical and alternative RAAS pathways. These findings carry practical implications for managing fluid-responsive conditions and electrolyte balance—diuretic-induced RAAS activation may explain adaptive physiological changes observed clinically, whilst repeated furosemide use could theoretically exacerbate conditions sensitive to angiotensin II signalling (cardiovascular remodelling, salt retention). Serum equilibrium analysis offers equine practitioners a reliable, practical alternative to traditional sampling methods for monitoring RAAS status in horses receiving chronic diuretic therapy or presenting with conditions where RAAS dysregulation is clinically relevant.
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Practical Takeaways
- •Furosemide use in horses activates compensatory hormonal responses; practitioners should be aware of RAAS activation when using this diuretic, particularly in horses with cardiac or renal conditions where RAAS status is clinically relevant
- •Equilibrium analysis provides a practical laboratory method for monitoring RAAS activity in horses when clinical assessment of diuretic effects warrants hormonal evaluation
- •The 4-hour peak in RAAS peptides suggests timing considerations for repeat dosing or monitoring of hemodynamic effects following furosemide administration
Key Findings
- •Equilibrium analysis is a practical and reliable method for measuring RAAS peptides in horses, with high correlation (r=0.92-0.95) to protease-inhibited samples
- •Single IV dose of furosemide (1 mg/kg) significantly elevated multiple angiotensin peptides at 4 hours post-administration, including AngI, AngII, AngIII, AngIV, and Ang1-5
- •AngII showed the greatest increase following furosemide, rising from baseline median of 7.5 pmol/L to 33.7 pmol/L (P=0.0008)
- •Furosemide activated both classical and alternative RAAS pathways in healthy thoroughbreds, demonstrating transient RAAS peptide activation similar to other species