The classical and alternative circulating renin‐angiotensin system in normal dogs and dogs with stage B1 and B2 myxomatous mitral valve disease
Abstract Background The behavior of the comprehensive circulating renin‐angiotensin system (RAS) in dogs with myxomatous mitral valve disease (MMVD) before to the onset of congestive heart failure remains largely unexplored. Hypothesis/Objectives The classical and alternative RAS activity and aldost...
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Wiley
2023-05-01
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Series: | Journal of Veterinary Internal Medicine |
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Online Access: | https://doi.org/10.1111/jvim.16687 |
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author | Hillary H. Hammond Marisa K. Ames Oliver Domenig Brian A. Scansen Nuen Tsang Yang Machelle D. Wilson Erin Sunshine Kaitlyn Brunk Allison Masters |
author_facet | Hillary H. Hammond Marisa K. Ames Oliver Domenig Brian A. Scansen Nuen Tsang Yang Machelle D. Wilson Erin Sunshine Kaitlyn Brunk Allison Masters |
author_sort | Hillary H. Hammond |
collection | DOAJ |
description | Abstract Background The behavior of the comprehensive circulating renin‐angiotensin system (RAS) in dogs with myxomatous mitral valve disease (MMVD) before to the onset of congestive heart failure remains largely unexplored. Hypothesis/Objectives The classical and alternative RAS activity and aldosterone concentrations will be significantly higher in dogs with American College of Veterinary Internal Medicine (ACVIM) stage B2 MMVD compared to normal dogs and dogs with ACVIM stage B1 MMVD. Animals One‐hundred seventeen client‐owned dogs (normal = 60; B1 = 31; B2 = 26). Methods Prospective observational study. Angiotensin peptides (AP) and aldosterone concentrations were measured using liquid chromatography and mass spectrometry. Angiotensin converting enzymes 1 and 2 (ACE, ACE2) and renin activity surrogates were calculated from AP concentrations. Equilibrium dialysis (ED) and immediate protease inhibition (PI) methods of AP quantification were compared in 14 healthy dogs. Results Core RAS activity and aldosterone concentrations did not differ among the 3 groups. However, the balance between the alternative and classical RAS differed, with dogs with stage B2 MMVD having significantly higher ACE2 activity surrogate (ACE2surr) when compared to normal dogs (adjusted P = .02; ratio of medians for ACE2surr [B2:normal], 1.89; 95% confidence interval [CI]: 1.4‐2.6). The ED and PI methods of AP quantification were highly correlated (AngI, r = .9, P < .0001; AngII, r = .8, P = .001). Conclusions and Clinical Importance Circulating alternative RAS activity, specifically the surrogate measure of ACE2 activity, was increased in dogs with stage B2 MMVD as compared to normal dogs. Equilibrium dialysis results are analogous to immediate protease inhibition in dogs. |
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issn | 0891-6640 1939-1676 |
language | English |
last_indexed | 2024-03-13T08:34:10Z |
publishDate | 2023-05-01 |
publisher | Wiley |
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series | Journal of Veterinary Internal Medicine |
spelling | doaj.art-9c23ec274cc842bfb0bef77f677122e42023-05-31T01:33:58ZengWileyJournal of Veterinary Internal Medicine0891-66401939-16762023-05-0137387588610.1111/jvim.16687The classical and alternative circulating renin‐angiotensin system in normal dogs and dogs with stage B1 and B2 myxomatous mitral valve diseaseHillary H. Hammond0Marisa K. Ames1Oliver Domenig2Brian A. Scansen3Nuen Tsang Yang4Machelle D. Wilson5Erin Sunshine6Kaitlyn Brunk7Allison Masters8Department of Clinical Sciences Colorado State University College of Veterinary Medicine and Biomedical Sciences Fort Collins Colorado USADepartment of Clinical Sciences Colorado State University College of Veterinary Medicine and Biomedical Sciences Fort Collins Colorado USAClinical and Translational Science Center, Department of Public Health Sciences, Division of Biostatistics University of California Sacramento California USADepartment of Clinical Sciences Colorado State University College of Veterinary Medicine and Biomedical Sciences Fort Collins Colorado USAAttoquant Diagnostics GmbH Vienna AustriaAttoquant Diagnostics GmbH Vienna AustriaDepartment of Clinical Sciences Colorado State University College of Veterinary Medicine and Biomedical Sciences Fort Collins Colorado USADepartment of Clinical Sciences Colorado State University College of Veterinary Medicine and Biomedical Sciences Fort Collins Colorado USADepartment of Clinical Sciences Colorado State University College of Veterinary Medicine and Biomedical Sciences Fort Collins Colorado USAAbstract Background The behavior of the comprehensive circulating renin‐angiotensin system (RAS) in dogs with myxomatous mitral valve disease (MMVD) before to the onset of congestive heart failure remains largely unexplored. Hypothesis/Objectives The classical and alternative RAS activity and aldosterone concentrations will be significantly higher in dogs with American College of Veterinary Internal Medicine (ACVIM) stage B2 MMVD compared to normal dogs and dogs with ACVIM stage B1 MMVD. Animals One‐hundred seventeen client‐owned dogs (normal = 60; B1 = 31; B2 = 26). Methods Prospective observational study. Angiotensin peptides (AP) and aldosterone concentrations were measured using liquid chromatography and mass spectrometry. Angiotensin converting enzymes 1 and 2 (ACE, ACE2) and renin activity surrogates were calculated from AP concentrations. Equilibrium dialysis (ED) and immediate protease inhibition (PI) methods of AP quantification were compared in 14 healthy dogs. Results Core RAS activity and aldosterone concentrations did not differ among the 3 groups. However, the balance between the alternative and classical RAS differed, with dogs with stage B2 MMVD having significantly higher ACE2 activity surrogate (ACE2surr) when compared to normal dogs (adjusted P = .02; ratio of medians for ACE2surr [B2:normal], 1.89; 95% confidence interval [CI]: 1.4‐2.6). The ED and PI methods of AP quantification were highly correlated (AngI, r = .9, P < .0001; AngII, r = .8, P = .001). Conclusions and Clinical Importance Circulating alternative RAS activity, specifically the surrogate measure of ACE2 activity, was increased in dogs with stage B2 MMVD as compared to normal dogs. Equilibrium dialysis results are analogous to immediate protease inhibition in dogs.https://doi.org/10.1111/jvim.16687angiotensin converting enzyme 2equilibrium dialysisheart failureneurohormonesprotease inhibitionurine aldosterone to creatinine ratio |
spellingShingle | Hillary H. Hammond Marisa K. Ames Oliver Domenig Brian A. Scansen Nuen Tsang Yang Machelle D. Wilson Erin Sunshine Kaitlyn Brunk Allison Masters The classical and alternative circulating renin‐angiotensin system in normal dogs and dogs with stage B1 and B2 myxomatous mitral valve disease Journal of Veterinary Internal Medicine angiotensin converting enzyme 2 equilibrium dialysis heart failure neurohormones protease inhibition urine aldosterone to creatinine ratio |
title | The classical and alternative circulating renin‐angiotensin system in normal dogs and dogs with stage B1 and B2 myxomatous mitral valve disease |
title_full | The classical and alternative circulating renin‐angiotensin system in normal dogs and dogs with stage B1 and B2 myxomatous mitral valve disease |
title_fullStr | The classical and alternative circulating renin‐angiotensin system in normal dogs and dogs with stage B1 and B2 myxomatous mitral valve disease |
title_full_unstemmed | The classical and alternative circulating renin‐angiotensin system in normal dogs and dogs with stage B1 and B2 myxomatous mitral valve disease |
title_short | The classical and alternative circulating renin‐angiotensin system in normal dogs and dogs with stage B1 and B2 myxomatous mitral valve disease |
title_sort | classical and alternative circulating renin angiotensin system in normal dogs and dogs with stage b1 and b2 myxomatous mitral valve disease |
topic | angiotensin converting enzyme 2 equilibrium dialysis heart failure neurohormones protease inhibition urine aldosterone to creatinine ratio |
url | https://doi.org/10.1111/jvim.16687 |
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