ACE and ACE2 catalytic activity in the fecal content along the gut

Abstract

BackgroundAngiotensin‐converting enzyme (ACE) and ACE2 are two major enzymes of the renin–angiotensin–aldosterone system (RAAS), which control the formation/degradation of angiotensin (Ang) II and Ang1‐7, regulating their opposite effects. We aimed at evaluating the catalytic activity of ACE and ACE2 in the intestinal content and corresponding intestinal tissue along the gut of Wistar Han rats.MethodsPortions of the ileum, cecum, proximal colon, and distal colon, and the corresponding intestinal content were collected from Wistar Han rats. Enzyme activity was evaluated by fluorometric assays using different substrates: Hippuryl‐His‐Leu for ACE‐C‐domain, Z‐Phe‐His‐Leu for ACE‐N‐domain, and Mca‐APK(Dnp) for ACE2. ACE and ACE2 concentration was assessed by ELISA. Ratios concerning concentrations and activities were calculated to evaluate the balance of the RAAS. Statistical analysis was performed using Friedman test followed by Dunn's multiple comparisons test or Wilcoxon matched‐pairs test whenever needed.Key ResultsACE and ACE2 are catalytically active in the intestinal content along the rat gut. The ACE N‐domain shows higher activity than the C‐domain both in the intestinal content and in the intestinal tissue. ACE and ACE2 are globally more active in the intestinal content than in the corresponding intestinal tissue. There was a distal‐to‐proximal prevalence of ACE2 over ACE in the intestinal tissue.Conclusions & InferencesThis work is the first to report the presence of catalytically active ACE and ACE2 in the rat intestinal content, supporting future research on the regulatory role of the intestinal RAAS on gut function and a putative link to the microbiome.

Biological sex differences in renin angiotensin system enzymes ACE and ACE2 regulate normal tissue response to radiation injury

“…Of note, ACE2 agonism with DIZE was capable of rescuing male rats from morbidity due to GI-ARS. Future studies will be necessary to evaluate the potential dysregulation of the gut RAS, but recent studies suggest intestinal ACE and ACE2 may play a regulatory role in the intestine (Ferreira-Duarte et al, 2023).…”