Effect of angiotensin receptor blockers and angiotensin converting enzyme 2 on plasma equilibrium angiotensin peptide concentrations in dogs with heart disease

Abstract Background The pathophysiology of heart failure involves maladaptive angiotensin peptides (APs) and enzymes, including angiotensin 2 (AT2) and angiotensin converting enzyme (ACE), as well as recently described alternative components, such as angiotensin 1‐7 (Ang1‐7) and angiotensin converting enzyme 2 (ACE2). The relative effects of different neurohormonal‐targeting drugs on balance of APs in dogs with heart disease are unknown. Hypothesis/Objectives Plasma AP concentrations differ in dogs receiving angiotensin converting enzyme inhibitors (ACEIs) vs angiotensin receptor blockers (ARBs) and recombinant human ACE2 (rhACE2) will further increase these differences. Animals Eight dogs with degenerative mitral valve disease (DMVD). Methods Prospective open‐label trial. Equilibrium concentrations of APs from plasma during PO ACEI treatment and then after 14 days of PO ARB treatment using telmisartan were measured using liquid chromatography‐tandem mass spectroscopy before and after in vitro incubation with rhACE2. Results Concentration of Ang1‐7 was increased during ARB treatment (Ang1‐7: 443 pg/mL; 95% confidence interval [CI] = 247‐794 pg/mL) vs ACEI (Ang1‐7: 182 pg/mL; 95% CI = 66.2‐503 pg/mL; P = .01). Incubation with rhACE2 decreased traditional APs while increasing beneficial alternative APs, and Ang1‐7 was significantly higher in the ARB + rhACE2 (880 pg/mL; 95% CI = 560‐1383 pg/mL) vs ACEI + rhACE2 (455 pg/mL; 95% CI = 188‐1104 pg/mL; P = .03) group. The most favorable theoretical AP profile was achieved in the ARB + rhACE2 group. Conclusions and Clinical Importance The AP profile during telmisartan treatment is associated with higher plasma Ang1‐7 as compared with during ACEI. This favorable shift is potentiated in vitro by combination of ARB + rhACE2. These data support potential AP‐targeting strategies and drugs in dogs with DMVD.