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

J Vet Intern Med. 2021 Jan;35(1):33-42. doi: 10.1111/jvim.15948. Epub 2020 Nov 2.

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.

Keywords: angiotensin 1-7; angiotensin II; cardiomyopathy; renin-angiotensin-aldosterone-system.

Publication types

  • Clinical Trial, Veterinary

MeSH terms

  • Angiotensin Receptor Antagonists*
  • Angiotensin-Converting Enzyme 2
  • Angiotensin-Converting Enzyme Inhibitors*
  • Animals
  • Cat Diseases* / drug therapy
  • Cats
  • Heart Diseases* / veterinary
  • Peptides
  • Prospective Studies
  • Renin-Angiotensin System

Substances

  • Angiotensin Receptor Antagonists
  • Angiotensin-Converting Enzyme Inhibitors
  • Peptides
  • Angiotensin-Converting Enzyme 2