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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Main Authors: Hillary H. Hammond, Marisa K. Ames, Oliver Domenig, Brian A. Scansen, Nuen Tsang Yang, Machelle D. Wilson, Erin Sunshine, Kaitlyn Brunk, Allison Masters
Format: Article
Language:English
Published: Wiley 2023-05-01
Series:Journal of Veterinary Internal Medicine
Subjects:
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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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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