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.

Carnosine to Combat Novel Coronavirus (nCoV): Molecular Docking and Modeling to Cocrystallized Host Angiotensin-Converting Enzyme 2 (ACE2) and Viral Spike Protein

“…COVID-19 is one such disease and Soto et al make a case that the Angiotensin (1-7) (A (1-7)) has a major protective effect in COVID-19 oxidative damage and lung injury [43]. Upregulated ACE2 may be protective too, but it is also a major means of nCoV entry into host cells and this process results in its downregulation [12,13,44,45]. Gul et al discussed the growing evidence that shifting the equilibrium to the A (1-7)/ACE2 receptor access would be more favorable [46].…”

Suspected primary hyperreninism in a cat with malignant renal sarcoma and global renin‐angiotensin‐aldosterone system upregulation

“…The plasma equilibrium concentrations of 6 different RAAS angiotensin peptides, including AngI, AngII, AngIII, AngIV, Ang(1‐7), and Ang(1‐5) were quantified by liquid chromatography‐mass spectrometry/mass spectroscopy performed at a commercial laboratory using previously validated and described methods. 8 , 10 Angiotensin‐based markers for renin (PRA‐S) and angiotensin converting enzyme (ACE‐S) were derived from AngII and AngI concentrations by calculating their sum and ratio, respectively, as described by the analytical laboratory. 11 , 12 …”

“… 7 Some RAAS‐inhibiting agents, such as telmisartan, may exert beneficial affects not only by impeding the traditional RAAS, but also by diverting RAAS metabolites to these alternative beneficial pathways. 7 , 8 …”

“…Consideration of both classical and alternative RAAS pathways is crucial for the understanding and management of disease. Comprehensive RAAS profiling has been performed in healthy cats, as well as in cats with cardiomyopathy 8 , 9 or systemic hypertension. 9 Results of these studies suggest that among cats with cardiomyopathy, RAAS profiles remain unchanged compared to healthy cats during the early and asymptomatic phase.…”

“…9 Results of these studies suggest that among cats with cardiomyopathy, RAAS profiles remain unchanged compared to healthy cats during the early and asymptomatic phase. 8 In contrast, cats with more advanced disease and congestive heart failure show significant and nonspecific RAAS upregulation, with the most marked RAAS perturbations occurring in furosemide‐treated cats. 9 Among cats with systemic hypertension, untreated cats did not differ from healthy controls, whereas significant nonspecific RAAS upregulation was observed in the subset of cats receiving amlodipine.…”