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 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 (ACE2_surr ) when compared to normal dogs (adjusted P = .02; ratio of medians for ACE2_surr [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.

Keywords: angiotensin converting enzyme 2; equilibrium dialysis; heart failure; neurohormones; protease inhibition; urine aldosterone to creatinine ratio.