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

Abstract

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 (CMnoRAASi) and then after 14 days of PO telmisartan (CMARB). Plasma APs also were measured after in vitro incubation with rhACE2. Results: No significant differences were found between healthy and CMnoRAASi groups. Concentrations of several APs, including angiotensin I (AT1) and angiotensin II (AT2) were significantly different between CMnoRAASi and CMARB groups. Incubation with rhACE2 decreased AT1 and AT2 in both groups. The geometric mean concentration of Ang1-7 was significantly higher in CMARB (4.9 pg/mL; 95% confidence interval [CI], 3.7-6.4 pg/mL) vs CMnoRAASi (3.2 pg/mL; 95% CI, 2.2-4.7 pg/mL; P =.01) and in CMARB + ACE2 (5.0 pg/mL; 95% CI, 3.9-6.4 pg/mL) vs CMnoRAASi + 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 CMARB + 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.