FREE SHIPPING over $40
OVER 10000 FIVE-STAR REVIEWS
5% OFF ALL SUBSCRIPTIONS
100% HAPPINESS GUARANTEE
Analyze Diet
0
Journal of veterinary internal medicine2024; doi: 10.1111/jvim.17208

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

Abstract: Furosemide, a commonly used diuretic, activates the renin-angiotensin-aldosterone system (RAAS) in other species. Little is known about RAAS peptide activation in horses. Objective: 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. Methods: 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: 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.
© 2024 The Author(s). Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.
Get Full Text
Publication Date: 2024-10-22 PubMed ID: 39434560DOI: 10.1111/jvim.17208Google Scholar: Lookup
The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
LinkedInCopy
  • Journal Article

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

This study investigates the effects of the diuretic Furosemide on the renin-angiotensin-aldosterone system (RAAS) of Thoroughbred horses, concluding that Furosemide induces an increase in hormones linked with both the traditional and alternate RAAS pathways.

Objectives and Hypothesis

  • The intention of this research was to use equilibrium analysis to quantify the RAAS activity in Thoroughbred horses and to observe the changes that take place after administering a single dosage of Furosemide.
  • The team proposed that the introduction of Furosemide would lead to a short-term surge in RAAS peptide activity within the horses.

Methods

  • Fourteen healthy adult thoroughbreds were used as test subjects. All horses came from a university teaching herd.
  • In a crossover study design, horses were given either an intravenous (IV) dose of Furosemide or saline.
  • Samples treated with protease inhibitors were compared with the equilibrium analysis samples through a Deming regression analysis.
  • At time intervals of 0, 0.25, 0.5, 4 and 24 hours after administration, the hormones of the RAAS were evaluated using equilibrium analysis.
  • A mixed effects model was employed for comparison purposes.

Results

  • There was a high correlation between the results gathered from protease inhibition and equilibrium analysis, especially with regards to the angiotensin I (AngI) and angiotensin II (AngII) peptides.
  • Before the study began, the RAAS peptide levels were below detectable limits, the only identifiable presence being AngII.
  • The application of Furosemide led to a noticeable increase in several peptides after four hours, namely AngI, AngII, angiotensin III (AngIII), angiotensin IV (AngIV) and angiotensin 1-5 (Ang1-5).

Conclusions

  • The researchers summarized that Furosemide does indeed result in an elevation in hormone levels associated with both classical and alternative RAAS pathways.
  • It was also found that serum equilibrium analysis is a practical method for studying RAAS in horses.

Cite This Article

APA
Lehman ML, Domenig O, Ames MK, Morgan JM. (2024). Effect of furosemide on comprehensive renin-angiotensin-aldosterone system activity of Thoroughbred horses. J Vet Intern Med. https://doi.org/10.1111/jvim.17208

Publication

Journal of veterinary internal medicine
ISSN: 1939-1676
NlmUniqueID: 8708660
Country: United States
Language: English

Researcher Affiliations

Lehman, Mallory L
  • Veterinary Medical Teaching Hospital, School of Veterinary Medicine, University of California-Davis, Davis, California, USA.
Domenig, Oliver
  • Attoquant Diagnostics GmbH, Vienna, Austria.
Ames, Marisa K
  • Department of Medicine and Epidemiology, School of Veterinary Medicine, University of California-Davis, Davis, California, USA.
Morgan, Jessica M
  • Department of Medicine and Epidemiology, School of Veterinary Medicine, University of California-Davis, Davis, California, USA.

Grant Funding

  • 21-Q / UC Davis Center for Equine Health

References

This article includes 38 references
  1. Ames MK, Atkins CE, Pitt B. The renin‐angiotensin‐aldosterone system and its suppression.. J Vet Intern Med 2019;33(2):363‐382.
    doi: 10.1111/jvim.15454google scholar: lookup
  2. Wang J, Chen L, Chen B. Chronic activation of the renin‐angiotensin system induces lung fibrosis.. Sci Rep 2015;5:5.
    doi: 10.1038/srep15561google scholar: lookup
  3. Jia G, Aroor AR, Hill MA, Sowers JR. Role of renin‐angiotensin‐aldosterone system activation in promoting cardiovascular fibrosis and stiffness.. Hypertension 2018;72(3):537‐548.
    doi: 10.1161/hypertensionaha.118.11065google scholar: lookup
  4. Remuzzi G, Perico N, Macia M, Ruggenenti P. The role of renin‐angiotensin‐aldosterone system in the progression of chronic kidney disease.. Kidney Int Suppl 2005;68:S57‐S65.
  5. Magalhaes GS, Rodrigues‐Machado MDG, Motta‐Santos D, Campagnole‐Santos MJ, Santos RAS. Activation of ang‐(1‐7)/mas receptor is a possible strategy to treat coronavirus (SARS‐CoV‐2) infection.. Front Physiol 2020;11:11.
    doi: 10.3389/fphys.2020.00730google scholar: lookup
  6. Cristina Simões Silva A, Lanza K, Andrade Palmeira V, Braga Costa L, Flynn JT. 2021 update on the renin‐angiotensin‐aldosterone system in pediatric kidney disease and its interactions with coronavirus.. Pediatr Nephrol 2021;36(6):1407‐1426.
    doi: 10.1007/s00467-020-04759-1google scholar: lookup
  7. Larouche‐Lebel É, Loughran KA, Oyama MA. Plasma and tissue angiotensin‐converting enzyme 2 activity and plasma equilibrium concentrations of angiotensin peptides in dogs with heart disease.. J Vet Intern Med 2019;33(4):1571‐1584.
    doi: 10.1111/jvim.15548google scholar: lookup
  8. Adin DB, Spalla M, Walden H, Gruntmeir J, Hernandez JA, Long M. Angiotensin‐converting enzyme 2 in dogs with Dirofilaria immitis.. Parasit Vectors 2023;16(1):145.
    doi: 10.1186/s13071-023-05649-9google scholar: lookup
  9. McKeever KH, Hinchcliff KW, Schmall LM, Reed SM, Lamb DR, Muir WW. Plasma renin activity and aldosterone and vasopressin concentrations during incremental treadmill exercise in horses.. Am J Vet Res 1992;53(8):1290‐1293.
  10. Muñoz A, Esgueva M, Gómez‐Díez M, Serrano‐Caballero JM, Castejón‐Riber C, Serrano‐Rodríguez JM. Modulation of acute transient exercise‐induced hypertension after oral administration of four angiotensin‐converting enzyme inhibitors in normotensive horses.. Vet J 2016;208:33‐37.
    doi: 10.1016/j.tvjl.2015.10.036google scholar: lookup
  11. Muir WW, Sams RA, Hubbell JA, Hinchcliff KW, Gadawski J. Effects of enalapril on cardiorespiratory, hemodynamic, and hematologic variables in exercising horses.. Am J Vet Res 2001;62(7):1008‐1013.
    doi: 10.2460/ajvr.2001.62.1008google scholar: lookup
  12. De Mello Costa MF, Ronchi FA, Yoonsuh J. ACE activity post‐race is influenced by furosemide administration.. Comp Exerc Physiol 2018;14(2):119‐125.
    doi: 10.3920/cep170032google scholar: lookup
  13. Muñoz A, Riber C, Trigo P, Castejón‐Riber C, Castejón FM. Dehydration, electrolyte imbalances and renin‐angiotensin‐aldosterone‐vasopressin axis in successful and unsuccessful endurance horses.. Equine Vet J 2010;42(SUPPL. 38):83‐90.
    doi: 10.1111/j.2042-3306.2010.00211.xgoogle scholar: lookup
  14. Dembek KA, Onasch K, Hurcombe SDA. Renin‐angiotensin‐aldosterone system and hypothalamic‐pituitary‐adrenal axis in hospitalized newborn foals.. J Vet Intern Med 2013;27(2):331‐338.
    doi: 10.1111/jvim.12043google scholar: lookup
  15. Holbrook T, Lester G, Sleeper M, Adin D. Renin‐angiotensin‐aldosterone system profiling in horses before and after exercise.. J Vet Intern Med 2021;35(6):2975‐2976A.
  16. Potter BM, Ames MK, Hess A, Poglitsch M. Comparison between the effects of torsemide and furosemide on the renin‐angiotensin‐aldosterone system of normal dogs.. J Vet Cardiol 2019;26:51‐62.
    doi: 10.1016/j.jvc.2019.11.003google scholar: lookup
  17. Kammerl MC, Nüsing RM, Schweda F. Pharmacodynamics and drug action: low sodium and furosemide‐induced stimulation of the renin system in man is mediated by cyclooxygenase 2.. Clin Pharmacol Ther 2001;70(5):468‐474.
    doi: 10.1067/mcp.2001.119720google scholar: lookup
  18. Lantis AC, Ames MK, Atkins CE, Defrancesco TC, Keene BW, Werre SR. Aldosterone breakthrough with benazepril in furosemide‐activated renin‐angiotensin‐aldosterone system in normal dogs.. J Vet Pharmacol Ther 2015;38(1):65‐73.
    doi: 10.1111/jvp.12154google scholar: lookup
  19. Lantis AC, Atkins CE, DeFrancesco TC, Keene BW, Werre SR. Effects of furosemide and the combination of furosemide and the labeled dosage of pimobendan on the circulating renin‐angiotensin‐aldosterone system in clinically normal dogs.. Am J Vet Res 2011;72(12):1646‐1651.
    doi: 10.2460/ajvr.72.12.1646google scholar: lookup
  20. Kovarik JJ, Antlanger M, Domenig O. Molecular regulation of the renin‐angiotensin system in haemodialysis patients.. Nephrol Dial Transplant 2015;30(1):115‐123.
    doi: 10.1093/ndt/gfu265google scholar: lookup
  21. Hammond HH, Ames MK, Domenig O. The classical and alternative circulating renin‐angiotensin system in normal dogs and dogs with stage B1 and B2 myxomatous mitral valve disease.. J Vet Intern Med 2023;37(3):875‐886.
    doi: 10.1111/jvim.16687google scholar: lookup
  22. May ML, Nolen‐Walston RD, Utter ME, Boston RC. Comparison of hematologic and biochemical results on blood obtained by jugular venipuncture as compared with intravenous catheter in adult horses.. J Vet Intern Med 2010;24(6):1462‐1466.
    doi: 10.1111/j.1939-1676.2010.0582.xgoogle scholar: lookup
  23. Domenig O, Manzel A, Grobe N. Neprilysin is a mediator of alternative renin‐angiotensin‐system activation in the murine and human kidney.. Sci Rep 2016;6:6.
    doi: 10.1038/srep33678google scholar: lookup
  24. Basu R, Poglitsch M, Yogasundaram H, Thomas J, Rowe BH, Oudit GY. Roles of angiotensin peptides and recombinant human ACE2 in heart failure.. J Am Coll Cardiol 2017;69:805‐819.
  25. European Medicines Agency. Committee for Medicinal Products for human use (CHMP). Guideline on Bioanalytical Method Validation.. 1922.
  26. Tofé E, Muñoz A, Castejón F. Behavior of renin angiotensin aldosterone axis during pulling exercises in euhydrated and dehydrated horses.. Res Vet Sci 2013;95(2):616‐622.
    doi: 10.1016/j.rvsc.2013.02.012google scholar: lookup
  27. Hollis AR, Boston RC, Corley KTT. Plasma aldosterone, vasopressin and atrial natriuretic peptide in hypovolaemia: a preliminary comparative study of neonatal and mature horses.. Equine Vet J 2008;40(1):64‐69.
    doi: 10.2746/042516407x235795google scholar: lookup
  28. Maron BA, Leopold JA. The role of the renin‐angiotensin‐aldosterone system in the pathobiology of pulmonary arterial hypertension (2013 Grover Conference series).. Pulm Circ 2014;4(2):200‐210.
    doi: 10.1086/675984google scholar: lookup
  29. Cooley JL, Hinchcliff KW, McKeever KH, Lamb DR, Muir WW. Effect of furosemide on plasma atrial natriuretic peptide and aldosterone concentrations and renin activity in running horses.. Am J Vet Res 1994;55(2):273‐277.
  30. Baffour‐Awuah B, Man M, Goessler KF. Effect of exercise training on the renin–angiotensin–aldosterone system: a meta–analysis.. J Hum Hypertens 2023;38:89‐101.
    doi: 10.1038/s41371-023-00872-4google scholar: lookup
  31. Johansson AM, Gardner SY, Levine JF. Pharmacokinetics and pharmacodynamics of furosemide after oral administration to horses.. J Vet Intern Med 2004;18(5):739‐743.
    doi: 10.1111/j.1939-1676.2004.tb02614.xgoogle scholar: lookup
  32. Hinchcliff KW, Couetil LL, Knight PK. Exercise induced pulmonary hemorrhage in horses: American College of Veterinary Internal Medicine Consensus Statement.. J Vet Intern Med 2015;29(3):743‐758.
    doi: 10.1111/jvim.12593google scholar: lookup
  33. Hori Y, Takusagawa F, Ikadai H, Uechi M, Hoshi F, Higuchi SI. Effects of oral administration of furosemide and torsemide in healthy dogs.. Am J Vet Res 2007;68(10):1058‐1063.
    doi: 10.2460/ajvr.68.10.1058google scholar: lookup
  34. Clarke LL, Ganjam VK, Fichtenbaum B, Hatfield D, Garner HE. Effect of feeding on renin‐angiotensin‐aldosterone system of the horse.. Am J Physiol 1988;254(3):R524‐R530.
    doi: 10.1152/ajpregu.1988.254.3.r524google scholar: lookup
  35. Freestone JF, Carlson GP, Harrold DR, Church G. Influence of furosemide treatment on fluid and electrolyte balance in horses.. Am J Vet Res 1988;49(11):1899‐1902.
  36. Hinchcliff KW, Muir WW. Pharmacology of furosemide in the horse: a review.. J Vet Intern Med 1991;5(4):211‐218.
    doi: 10.1111/j.1939-1676.1991.tb00951.xgoogle scholar: lookup
  37. Divers TJ. Acute kidney injury and renal failure in horses.. Vet Clin North Am Equine Pract 2022;38(1):13‐24.
    doi: 10.1016/j.cveq.2021.11.002google scholar: lookup
  38. van Galen G, Divers TJ, Savage V, Schott HC, Siwinska N. ECEIM consensus statement on equine kidney disease.. J Vet Intern Med 2024;38:2008‐2025.
    doi: 10.1111/jvim.17101google scholar: lookup

Citations

This article has been cited 1 times.
  1. Holbrook T, Hernandez J, McCarrel T, Lester G, Sleeper M, Domenig O, Adin D. Renin-Angiotensin-Aldosterone System Profiling in Horses Before and After Exercise. J Vet Intern Med 2025 Mar-Apr;39(2):e70036.
    doi: 10.1111/jvim.70036pubmed: 40048547google scholar: lookup
Subscribe to our newsletter
Join 99,780 horse owners like you who receive our email updates on horse health and nutrition.