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 aldosterone concentrations will be significantly higher in dogs with American College of Veterinary Internal Medicine (ACVIM) stage B2&#x2009;MMVD compared to normal dogs and dogs with ACVIM stage B1&#x2009;MMVD. ANIMALS: One-hundred seventeen client-owned dogs (normal&#xa0;=&#xa0;60; B1&#xa0;=&#xa0;31; B2&#xa0;=&#xa0;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&#x2009;MMVD having significantly higher ACE2 activity surrogate (ACE2) when compared to normal dogs (adjusted P&#xa0;=&#xa0;.02; ratio of medians for ACE2[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&#xa0;=&#xa0;.9, P&#x2009;<&#x2009;.0001; AngII, r&#xa0;=&#xa0;.8, P&#xa0;=&#xa0;.001). CONCLUSIONS AND CLINICAL IMPORTANCE: Circulating alternative RAS activity, specifically the surrogate measure of ACE2 activity, was increased in dogs with stage B2&#x2009;MMVD as compared to normal dogs. Equilibrium dialysis results are analogous to immediate protease inhibition in dogs.