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

Background: Little is known about the effect of renin angiotensin aldosterone system-inhibiting (RAASi) drugs on alternative angiotensin peptides (APs) such as angiotensin 1-7 (Ang1-7), which are mediated by angiotensin-converting enzyme 2 (ACE2).

Hypothesis/objectives: Angiotensin receptor blockers (ARBs) would alter balance of APs and differences would be magnified in vitro by incubation of plasma samples with recombinant human ACE2 (rhACE2).

Animals: Six cats with cardiomyopathy (CM), 8 healthy cats.

Methods: Prospective open label trial. Plasma equilibrium concentrations of APs were measured in healthy cats as well as in CM cats that first received no RAASi drugs (CM ) and then after 14 days of PO telmisartan (CM ). Plasma APs also were measured after in vitro incubation with rhACE2.

Results: No significant differences were found between healthy and CM groups. Concentrations of several APs, including angiotensin I (AT1) and angiotensin II (AT2) were significantly different between CM and CM groups. Incubation with rhACE2 decreased AT1 and AT2 in both groups. The geometric mean concentration of Ang1-7 was significantly higher in CM (4.9 pg/mL; 95% confidence interval [CI], 3.7-6.4 pg/mL) vs CM (3.2 pg/mL; 95% CI, 2.2-4.7 pg/mL; P = .01) and in CM  + ACE2 (5.0 pg/mL; 95% CI, 3.9-6.4 pg/mL) vs CM  + ACE2 (3.0 pg/mL; 95% CI, 1.7-5.5 pg/mL; P = .01). The most favorable theoretical AP profile that maximized Ang1-7 and other alternative APs was CM  + ACE2.

Conclusions And Clinical Importance: Balance between traditional and alternative APs can be favorably shifted using ARBs and in vitro incubation with rhACE2. These data shed light on new AP-targeting strategies in cats with CM.