Angiotensin II (Ang II) regulates colon contraction, acting not only directly on smooth muscle but also indirectly, interfering with myenteric neuromodulation mediated by the activation of AT₁ /AT₂ receptors. In this article, we aimed to explore which mediators and cells were involved in Ang II-mediated colonic contraction in the TNBS-induced rat model of colitis. The contractile responses to Ang II were evaluated in distinct regions of the colon of control animals or animals with colitis in the absence and presence of different antagonists/inhibitors. Endogenous levels of Ang II in the colon were assessed by ELISA and the number of AT₁/AT₂ receptors by qPCR. Ang II caused AT₁ receptor-mediated colonic contraction that was markedly decreased along the colons of TNBS-induced rats, consistent with reduced AT₁ mRNA expression. However, the effect mediated by Ang II is much more intricate, involving (in addition to smooth muscle cells and nerve terminals) ICC and EGC, which communicate by releasing ACh and NO in a complex mechanism that changes colitis, unveiling new therapeutic targets.

Diabetes mellitus (DM) is a chronic progressive metabolic disorder associated with several gastrointestinal complications, affecting up to 75% of patients. Knowing that Angiotensin II (AngII) also regulates intestinal contraction, we decided to evaluate changes in ileum and colon histomorphometry and AngII reactivity in a rat model of DM. Streptozotocin (STZ, 55 mg/kg) was administered to induce DM to 24 adult male Wistar rats. Diabetic rats displayed all the characteristic signs of type 1 DM (T1DM) and fecal excretion increased about 4-fold over 14 days, while the excretion of controls remained unaltered. Compared to controls, diabetic ileum and colon presented an increase in both macroscopic (length, perimeter and weight) and microscopic (muscular wall thickness) parameters. Functionally, AngII-induced smooth muscle contraction was lower in diabetic rats, except in the distal colon. These differences in the contractile response to AngII may result from an imbalance between AngII type 1 (antagonized by candesartan, 10 nM) and type 2 receptors activation (antagonized by PD123319, 100 nM). Taken together, these results indicate that an early and refined STZ-induced T1DM rat model already shows structural remodelling of the gut wall and decreased contractile response to AngII, findings that may help to explain diabetic dysmotility.

Background: Angiotensin‐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.Methods: Portions 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 Results: ACE 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 & Inferences: This 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.

Gastrointestinal complications of diabetes are often overlooked, despite affecting up to 75% of patients. This study innovatively explores local glutathione levels and morphometric changes in the gut of Goto–Kakizaki (GK) rats, a type 2 diabetes animal model. Segments of the intestine, cecum, and colon were collected for histopathological analysis and glutathione quantification. A significant increase in the total thickness of the intestinal wall of GK rats was observed, particularly in the duodenum (1089.02 ± 39.19 vs. 864.19 ± 37.17 µm), ileum (726.29 ± 24.75 vs. 498.76 ± 16.86 µm), cecum (642.24 ± 34.15 vs. 500.97 ± 28.81 µm), and distal colon (1211.81 ± 51.32 vs. 831.71 ± 53.2 µm). Additionally, diabetic rats exhibited thickening of the muscular layers in all segments, except for the duodenum, which was also the only portion where the number of smooth muscle cells did not decrease. Moreover, myenteric neuronal density was lower in GK rats, suggesting neurological loss. Total glutathione levels were lower in all intestinal segments of diabetic rats (except duodenum), and the reduced/oxidized glutathione ratio (GSH/GSSG) was significantly decreased in GK rats, indicating increased oxidative stress. These findings strongly indicate that GK rats undergo significant intestinal remodeling, notable shifts in neuronal populations, and heightened oxidative stress—factors that likely contribute to the functional gastrointestinal alterations seen in diabetic patients.

Diabetes is a metabolic disorder characterized by chronic hyperglycemia, affecting between 0.21% and 1.24% of cats. While gastrointestinal complications are well-documented in human diabetic patients—affecting up to 75%—similar data in cats remain scarce. This study explores gastrointestinal alterations in diabetic cats using ultrasound and histopathological evaluations, alongside assessing owners’ perceptions of digestive issues. A brief survey was conducted with the owners of diabetic cats to document diabetes symptoms and any gastrointestinal changes. Following the survey, each cat underwent abdominal US, focusing on the digestive tract including the stomach, duodenum, jejunum, ileum, and colon. Additionally, histopathological analysis was conducted on necropsied diabetic cats. Thirteen domestic spayed diabetic cats with no prior gastrointestinal disease were included, with 83% showing at least one gastrointestinal issue reported by owners. All cats exhibited increased gastric, duodenal, and jejunal wall thickness, while the ileum and colon showed normal thickness. Histopathological evaluation revealed increased thickness of the muscular layers, inflammatory infiltrate, and collagen deposits in the whole length of the gastrointestinal tract. These findings suggest that diabetic cats may experience gastrointestinal remodeling, a phenomenon that, while well recognized in human diabetes, has not been adequately studied in feline patients.