Renin-Angiotensin Aldosterone System Modulation and Cardiovascular-Kidney-Metabolic Health

Similar to humans, the renin-angiotensin-aldosterone system (RAAS) plays a key role in regulating blood pressure and body fluid homeostasis in dogs and cats. The classical RAAS pathway, which involves the conversion of angiotensin I to angiotensin II by the angiotensin converting enzyme (ACE), leads to aldosterone production and associated maladaptive effects in cardiovascular and renal diseases. Recent studies have highlighted the alternative RAAS pathway, which counteracts these effects through angiotensin 1-7, promoting vasodilation and reducing inflammation. Beyond RAAS modulation, RAAS inhibitors have been shown to exert significant anti-inflammatory properties. This is particularly relevant given the American Heart Association's recent focus on Cardiovascular-Kidney-Metabolic (CKM) health, which emphasizes the interconnected risks of cardiovascular disease, chronic kidney disease (CKD), type 2 diabetes, and obesity. These conditions share common pathophysiological pathways, including chronic inflammation, oxidative stress, and metabolic dysregulation. Advances in biomedical research, including the development of adult stem cell-derived canine organoids, provide impetus to study the effects of RAAS modulators and new CVD drugs on CKM health, with a focus on epithelial inflammation within the context of One Health.