GI15 - Dysregulation of the Renin-angiotensin-aldosterone System (RAAS) and Dependent Electrolyte Transporters in Canine Chronic Inflammatory Enteropathy

Abstract: Background: Chronic diarrhea with intestinal electrolyte losses is a hallmark sign of canine chronic inflammatory enteropathy (CIE). Compared to hyponatremia predominating in human inflammatory bowel disease, hypokalemia is more prevalent in canine CIE suggesting species-specific counter-regulation of potential therapeutic relevance.

Objective: To investigate intestinal electrolyte transporters and components of the renin-angiotensin-aldosterone system (RAAS) in canine CIE.

Animals: Eight dogs with CIE and 12 healthy controls.

Methods: Serum RAAS fingerprint analysis was performed by mass spectrometry (5 CIE, 5 controls), and mRNA levels of electrolyte transporters and ATGR1 were quantified by RT-qPCR in ileal (7 CIE, 10 controls) and colonic (6 CIE, 12 controls) tissue biopsies. The results were compared between groups of dogs and tested for associations among each other and with clinical variables in CIE dogs.

Results: Components of traditional and alternative RAAS pathways were increased in CIE compared to health, with statistical significance for Ang I, Ang II, and Ang 1-7 (all P<0.037). Abundances of ileal (but not colonic) Na+/K+-ATPase, ENaC, and NHE3 (all P<0.023) mRNA (but not ATGR1) were increased in CIE.

Conclusions: Differential activation of ileal and colonic electrolyte transporters could be an efficient mechanism of sodium preservation in canine CIE, with the signaling mediated by alternative RAAS components and lack of AGTR1 dysregulation suggesting direct endocrine RAAS effects. Unchanged colonic electrolyte transporter expression in CIE dogs with marked diarrhea suggests the compensatory reserve of the colon is not activated and may reflect the dual role of moderate vs. high systemic Ang II levels.