FREE SHIPPING over $40
OVER 10000 FIVE-STAR REVIEWS
5% OFF ALL SUBSCRIPTIONS
100% HAPPINESS GUARANTEE
Analyze Diet
0
Journal of veterinary internal medicine2025; 39(2); e70036; doi: 10.1111/jvim.70036

Renin-Angiotensin-Aldosterone System Profiling in Horses Before and After Exercise.

Abstract: The impact of exercise on the classical and alternative renin-angiotensin-aldosterone system (RAAS) pathways has not been studied in horses. Objective: We hypothesized that exercise would activate both RAAS pathways and that endurance exercise would cause more activation of the classical pathway compared to short-duration, high-intensity exercise in horses. Methods: Twenty-five horses (21 client-owned and 4 research) were included in 4 exercise groups (10 Arabians, 50-mile ride [A-E]; 4 thoroughbreds, 1-mile treadmill exercise [TB-TM]; 5 thoroughbreds, 1-1/16th-mile race [TB-R]; and 6 quarter horses 330-500-yard race [QH-R]). Methods: Blood was collected before and after exercise. Equilibrium analysis was performed to measure serum RAAS metabolites and enzyme activities. The components of the RAAS pathways were compared before and after exercise. Post/pre-exercise ratios for each variable were compared among exercise groups. Data were reported as median (first, third quartiles; pre vs. post) and p < 0.05 was considered significant. Results: Exercise increased classical RAAS metabolites (pmol/L; angiotensin I, 2.5 [2.5, 2.5] vs. 8.2 [2.5, 19.0]; angiotensin II, 10.2 [6.0, 21.9] vs. 53.0 [37.4, 95.8]; aldosterone, 83.8 [53.4, 149.5] vs. 170.6 [112.2, 251.7]); alternative RAAS metabolites (pmol/L; angiotensin 1-7, 1.5 [1.5, 1.5] vs. 5.1 [1.5, 12.5]; angiotensin 1-5, 2.5 [2.5, 7.3] vs. 14.9 [9.0, 25.4]) and angiotensin-converting enzyme-2 activity (ng/mL; 16.6 [13.9, 20.4] vs. 25.2 [20.2, 33.0]; p < 0.001) for all horses. Angiotensin 1-7 ratios were higher for TB-R compared with TB-TM and A-E (p < 0.001). Conclusions: Both classical and alternative RAAS pathways increase after exercise in horses.
© 2025 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: 2025-03-06 PubMed ID: 40048547PubMed Central: PMC11884522DOI: 10.1111/jvim.70036Google 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 research investigates the effect of exercise on the renin-angiotensin-aldosterone system (RAAS) pathways in horses, hypothesizing that exercise would increase the activation of both classical and alternative RAAS pathways. The findings suggest that both these pathways increase after exercise in all horse types studied, with endurance exercises causing more activation of the classical RAAS pathway.

Research Methodology

  • Twenty-five horses, some client-owned and some research subjects, participated. They were grouped into four different exercise categories.
  • The categories included Arabians in a 50-mile ride, thoroughbreds in a 1-mile treadmill exercise, thoroughbreds in a 1-1/16th-mile race, and quarter horses in 330-500-yard races.
  • Blood samples were taken before and after the horses exercised. These samples were used to measure serum RAAS metabolites and enzyme activities and then compared to determine the changes in RAAS pathways due to the exertion.

Results

  • The results confirmed that exercise escalates both the classical and alternative RAAS pathways in horses.
  • This increase was evident in both RAAS metabolites and angiotensin-converting enzyme-2 activity across all the horses, regardless of the type of exercise they undertook.
  • However, the results showed that the ratios of angiotensin 1-7, an important component of the alternative RAAS pathway, were higher in thoroughbreds that raced compared to those engaged in treadmill exercise and the Arabians on a ride. This suggests that selective short-burst, high-intensity exercise like racing might lead to more activation of this alternative pathway.

Conclusion

  • Overall, the study confirmed its initial hypothesis that exercise activates both the classical and alternative RAAS pathways in horses. The results also hint towards the varying effects different types of exertion can have on these pathways.
  • This can have significant implications for horse health and training regimens. By understanding how different exercises impact physiological responses, trainers can optimize horse performance and overall wellbeing. Further research into these pathways could also potentially contribute to sport medicine and veterinary science.

Cite This Article

APA
Holbrook T, Hernandez J, McCarrel T, Lester G, Sleeper M, Domenig O, Adin D. (2025). Renin-Angiotensin-Aldosterone System Profiling in Horses Before and After Exercise. J Vet Intern Med, 39(2), e70036. https://doi.org/10.1111/jvim.70036

Publication

Journal of veterinary internal medicine
ISSN: 1939-1676
NlmUniqueID: 8708660
Country: United States
Language: English
Volume: 39
Issue: 2
Pages: e70036
PII: e70036

Researcher Affiliations

Holbrook, Todd
  • College of Veterinary Medicine, University of Florida, Gainesville, Florida, USA.
Hernandez, Jorge
  • College of Veterinary Medicine, University of Florida, Gainesville, Florida, USA.
McCarrel, Taralyn
  • College of Veterinary Medicine, University of Florida, Gainesville, Florida, USA.
Lester, Guy
  • College of Veterinary Medicine, University of Florida, Gainesville, Florida, USA.
Sleeper, Margaret
  • College of Veterinary Medicine, University of Florida, Gainesville, Florida, USA.
Domenig, Oliver
  • Attoquant Diagnostics, Vienna, Austria.
Adin, Darcy
  • College of Veterinary Medicine, University of Florida, Gainesville, Florida, USA.

MeSH Terms

  • Animals
  • Horses / blood
  • Horses / physiology
  • Renin-Angiotensin System / physiology
  • Physical Conditioning, Animal / physiology
  • Male
  • Female
  • Angiotensin I / blood
  • Aldosterone / blood
  • Peptidyl-Dipeptidase A / blood

Grant Funding

  • Florida Department of Business and Professional Regulation
  • AWD06761 / Racing Animal Medical Research
  • June Jacobs Endowed Chair in Equine Medicine, Oklahoma State University, College of Veterinary Medicine

Conflict of Interest Statement

Oliver Domenig is employed by Attoquant Diagnostics. Darcy Adin is a consultant for Ceva Santé Animale and Boehringer Ingelheim. The other authors declare no conflicts of interest.

References

This article includes 35 references
  1. Lavoie JL, Sigmund CD. Minireview: Overview of the Renin‐Angiotensin System—An Endocrine and Paracrine System. Endocrinology 144 (2003): 2179–2183.
    pubmed: 12746271
  2. Ames MK, Atkins CE, Pitt B. The Renin‐Angiotensin‐Aldosterone System and Its Suppression. Journal of Veterinary Internal Medicine 33 (2019): 363–382.
    pmc: PMC6430926pubmed: 30806496
  3. Ferrario CM, Groban L, Wang H. The Renin‐Angiotensin System Biomolecular Cascade: A 2022 Update of Newer Insights and Concepts. Kidney International. Supplement 12 (2022): 36–47.
    pmc: PMC9073260pubmed: 35529089
  4. Fyhrquist F, Saijonmaa O. Renin‐Angiotensin System Revisited. Journal of Internal Medicine 264 (2008): 224–236.
    pmc: PMC7166930pubmed: 18793332
  5. Ho JK, Nation DA. Cognitive Benefits of Angiotensin IV and Angiotensin‐(1–7): A Systematic Review of Experimental Studies. Neuroscience and Biobehavioral Reviews 92 (2018): 209–225.
    pmc: PMC8916541pubmed: 29733881
  6. Domenig O, Manzel A, Grobe N. Neprilysin Is a Mediator of Alternative Renin‐Angiotensin‐System Activation in the Murine and Human Kidney. Scientific Reports 6 (2016): 33678.
    pmc: PMC5030486pubmed: 27649628
  7. Welches WR, Santos RA, Chappell MC. Evidence That Prolyl Endopeptidase Participates in the Processing of Brain Angiotensin. Journal of Hypertension 9 (1991): 631–638.
    pubmed: 1653799
  8. Welches WR, Brosnihan KB, Ferrario CM. A Comparison of the Properties and Enzymatic Activities of Three Angiotensin Processing Enzymes: Angiotensin Converting Enzyme, Prolyl Endopeptidase and Neutral Endopeptidase 24.11. Life Sciences 52 (1993): 1461–1480.
    pubmed: 8387132
  9. Basu R, Poglitsch M, Yogasundaram H. Roles of Angiotensin Peptides and Recombinant Human ACE2 in Heart Failure. Journal of the American College of Cardiology 69 (2017): 805–819.
    pubmed: 28209222
  10. Adin D, Atkins C, Domenig O. Renin‐Angiotensin Aldosterone Profile Before and After Angiotensin‐Converting Enzyme‐Inhibitor Administration in Dogs With Angiotensin‐Converting Enzyme Gene Polymorphism. Journal of Veterinary Internal Medicine 34 (2020): 600–606.
    pmc: PMC7097578pubmed: 32112596
  11. Ziff OJ, Covic A, Goldsmith D. Calibrating the Impact of Dual RAAS Blockade on the Heart and the Kidney–Balancing Risks and Benefits. International Journal of Clinical Practice 70 (2016): 537–553.
    pubmed: 27278080
  12. Costa MFM, Ronchi FA, Ivanow A, Carmona AK, Casarini D, Slocombe RF. Association Between Circulating Angiotensin‐Converting Enzyme and Exercise‐Induced Pulmonary Haemorrhage in Thoroughbred Racehorses. Research in Veterinary Science 93 (2012): 993–994.
    pubmed: 22196974
  13. Magalhaes DM, Nunes-Silva A, Rocha GC. Two Protocols of Aerobic Exercise Modulate the Counter‐Regulatory Axis of the Renin‐Angiotensin System. Heliyon 6 (2020): e03208.
    pmc: PMC6970173pubmed: 31989052
  14. Gregorio JF, Magalhaes GS, Rodrigues-Machado MG. Angiotensin‐(1‐7)/Mas Receptor Modulates Anti‐Inflammatory Effects of Exercise Training in a Model of Chronic Allergic Lung Inflammation. Life Sciences 282 (2021): 119792.
    pubmed: 34229006
  15. de Alcantara Santos R, Guzzoni V, Silva KAS. Resistance Exercise Shifts the Balance of Renin‐Angiotensin System Toward ACE2/Ang 1‐7 Axis and Reduces Inflammation in the Kidney of Diabetic Rats. Life Sciences 287 (2021): 120058.
    pubmed: 34673118
  16. Munoz A, Riber C, Trigo P. Dehydration, Electrolyte Imbalances and Renin‐Angiotensin‐Aldosterone‐Vasopressin Axis in Successful and Unsuccessful Endurance Horses. Equine Veterinary Journal. Supplement 42 (2010): 83–90.
    pubmed: 21058987
  17. McKeever KH, Hinchcliff KW, Schmall LM. Plasma Renin Activity and Aldosterone and Vasopressin Concentrations During Incremental Treadmill Exercise in Horses. American Journal of Veterinary Research 53 (1992): 1290–1293.
    pubmed: 1510299
  18. Masri M, Freestone JF, Wolfsheimer KJ. Alterations in Plasma Volume, Plasma Constituents, Renin Activity and Aldosterone Induced by Maximal Exercise in the Horse. Equine Veterinary Journal. Supplement 22 (1990): 72–77.
    pubmed: 9259811
  19. Ward JL, Guillot E, Domenig O, Ware WA, Yuan L, Mochel JP. Circulating Renin‐Angiotensin‐Aldosterone System Activity in Cats With Systemic Hypertension or Cardiomyopathy. Journal of Veterinary Internal Medicine 36 (2022): 897–909.
    pmc: PMC9151484pubmed: 35285549
  20. De Mello Costa MF, Anderson GA, Davies HM. Effects of Acute Exercise on Angiotensin I‐Converting Enzyme (ACE) Activity in Horses. Equine Veterinary Journal 44 (2012): 487–489.
    pubmed: 21895753
  21. De Mello Costa MF, Anderson GA, Davies HM. Circulating Angiotensin Converting Enzyme in Endurance Horses: Effect of Exercise on Blood Levels and Its Value in Predicting Performance. Equine Veterinary Journal. Supplement 42 (2010): 152–154.
    pubmed: 21058998
  22. Haschke M, Schuster M, Poglitsch M. Pharmacokinetics and Pharmacodynamics of Recombinant Human Angiotensin‐Converting Enzyme 2 in Healthy Human Subjects. Clinical Pharmacokinetics 52 (2013): 783–792.
    pubmed: 23681967
  23. Nunes-Silva A, Rocha GC, Magalhaes DM, Vaz LN, Salviano de Faria MH, Simoes E Silva AC. Physical Exercise and ACE2‐Angiotensin‐(1‐7)‐Mas Receptor Axis of the Renin Angiotensin System. Protein and Peptide Letters 24 (2017): 809–816.
    pubmed: 28758593
  24. Bertagnolli M, Casali KR, De Sousa FB. An Orally Active Angiotensin‐(1‐7) Inclusion Compound and Exercise Training Produce Similar Cardiovascular Effects in Spontaneously Hypertensive Rats. Peptides 51 (2014): 65–73.
    pubmed: 24262271
  25. Echeverria-Rodriguez O, Gallardo-Ortiz IA, Del Valle-Mondragon L. Angiotensin‐(1‐7) Participates in Enhanced Skeletal Muscle Insulin Sensitivity After a Bout of Exercise. Journal of the Endocrine Society 4 (2020): bvaa007.
    pmc: PMC7039407pubmed: 32104748
  26. Shah A, Oh YB, Lee SH, Lim JM, Kim SH. Angiotensin‐(1‐7) Attenuates Hypertension in Exercise‐Trained Renal Hypertensive Rats. American Journal of Physiology. Heart and Circulatory Physiology 302 (2012): H2372–H2380.
    pubmed: 22467306
  27. Gallardo-Ortiz IA, Villalobos-Molina R, Echeverria-Rodriguez O. Potential Role of Angiotensin‐(1‐7) in the Improvement of Vascular Insulin Sensitivity After a Bout of Exercise. Experimental Physiology 105 (2020): 600–605.
    pubmed: 32125032
  28. Sandoval J, Del Valle-Mondragon L, Masso F. Angiotensin Converting Enzyme 2 and Angiotensin (1‐7) Axis in Pulmonary Arterial Hypertension. European Respiratory Journal 56 (2020): 1902416.
    pubmed: 32241831
  29. Wang YX, Liu ML, Zhang B, Fu EQ, Li ZC. Fasudil Alleviated Hypoxia‐Induced Pulmonary Hypertension by Stabilizing the Expression of Angiotensin‐(1‐7) in Rats. European Review for Medical and Pharmacological Sciences 20 (2016): 3304–3312.
    pubmed: 27467008
  30. Erickson BK, Erickson HH, Coffman JR. Pulmonary Artery, Aortic and Oesophageal Pressure Changes During High Intensity Treadmill Exercise in the Horse: A Possible Relation to Exercise‐Induced Pulmonary Haemorrhage. Equine Veterinary Journal. Supplement 22 (1990): 47–52.
    pubmed: 9259806
  31. Reef VB, Bain FT, Spencer PA. Severe Mitral Regurgitation in Horses: Clinical, Echocardiographic and Pathological Findings. Equine Veterinary Journal 30 (1998): 18–27.
    pubmed: 9458395
  32. Bonagura JD. Overview of Equine Cardiac Disease. Veterinary Clinics of North America. Equine Practice 35 (2019): 1–22.
    pubmed: 30871827
  33. Decloedt A, Borowicz H, Slowikowska M, Chiers K, van Loon G, Niedzwiedz A. Right Ventricular Function During Acute Exacerbation of Severe Equine Asthma. Equine Veterinary Journal 49 (2017): 603–608.
    pubmed: 28132404
  34. Lehman ML, Domenig O, Ames MK, Morgan JM. Effect of Furosemide on Comprehensive Renin‐Angiotensin‐Aldosterone System Activity of Thoroughbred Horses. Journal of Veterinary Internal Medicine 38 (2024): 3272–3280.
    pmc: PMC11586568pubmed: 39434560
  35. Clarke LL, Ganjam VK, Fichtenbaum B, Hatfield D, Garner HE. Effect of Feeding on Renin‐Angiotensin‐Aldosterone System of the Horse. American Journal of Physiology 254 (1988): R524–R530.
    pubmed: 3279828

Citations

This article has been cited 0 times.
Subscribe to our newsletter
Join 99,911 horse owners like you who receive our email updates on horse health and nutrition.