GI09 - Ileal and Colonic Renin-angiotensin-aldosterone System (RAAS) Receptor Dysregulation and Fibrosis Markers in Canine Chronic Enteropathy

Background: Upregulation of circulating RAAS components in dogs with chronic inflammatory enteropathy (CIE) has a signature similar to the phenomenon of “aldosterone breakthrough” and is associated with ileal, but not colonic, electrolyte transporter mRNA overexpression. Aldosterone promotes inflammation, fibrosis, and oxidant damage.

Objectives: Investigation of ileal and colonic RAAS receptors and fibrosis markers.
Animals: Archived tissue specimens from 7 CIE dogs and 6 apparently healthy controls.

Methods: Immunohistochemistry (IHC) evaluation for angiotensin II receptor type I (AGTR1) and type II (AGTR2), epithelial Na⁺-channel (ENaC), Mas (MasR) and mineralocorticoid receptor (MCR), collagen-1 and -3, and transforming growth factor-β (TGFβ). IHC-positive cells (quantified per 62,500 μm² in 5 randomly selected fields of ileal and colonic compartments) were evaluated in CIE vs. healthy dogs and were tested for associations with clinical and histologic findings.

Results: Increased AGTR1⁺ cell counts were inversely associated with AGTR2⁺ and MasR⁺ cells and were positively correlated with profibrotic markers (collagen-1, -3, and TGFβ). Local RAAS receptor positivity and fibrosis markers were linked to the severity of clinical signs and inflammatory and structural changes in the ileum and colon. However, MCR⁺ and ENaC⁺ cells differed spatially between both compartments and in relation to local RAAS receptors and fibrosis markers. These changes were more pronounced in dogs requiring immunomodulatory treatment (n=3) than with food-responsive disease (n=4).
Conclusions and clinical importance: Local RAAS receptor dysregulation in canine CIE reflects a shift towards proinflammatory and profibrotic pathways. Discrepancies with reported mRNA expression levels (e.g., for AGTR1) suggest a role of posttranslational variation.