Evaluation of Renin–Angiotensin–Aldosterone System Components and Enzymes in Systemically Hypertensive Cats Receiving Amlodipine

SIMPLE SUMMARY: High blood pressure (hypertension) is a common medical issue in cats. Amlodipine is a medication used to treat hypertension, but it might activate hormone systems that can be harmful in the long term. This preliminary study evaluated a hormone system called the renin–angiotensin–aldosterone system (RAAS) in cats with high blood pressure being treated with amlodipine compared to healthy cats with normal blood pressure, and found that hypertensive cats treated with amlodipine were RAAS activated. Since RAAS activation can have harmful long-term effects, including cardiac fibrosis (scar formation in the heart) and salt and water retention, medications to suppress the RAAS might be helpful in cats with high blood pressure that are treated with amlodipine. ABSTRACT: Background: Chronic renin–angiotensin–aldosterone system (RAAS) activation is harmful. Amlodipine activates RAAS in humans and dogs, but contradictory data exist for systemically hypertensive (SHT) cats. Hypothesis: Cats with SHT and chronic kidney disease treated with amlodipine (SHT/CKD-A) are RAAS activated. Animals: Client-owned cats: unmedicated normotensive (NT) cats (n = 9); SHT/CKD-A cats (n = 5) with median systolic blood pressure of 170 mmHg (vs. 195 mmHg, pre-treatment), chronic kidney disease, and receiving no RAAS-suppressive therapy. Methods: Serum was frozen (−80 °C) until RAAS analysis via equilibrium analysis. The RAAS variables (reported as median (minimum–maximum)) were compared between groups, using Mann–Whitney U test. Results: Angiotensin 1, angiotensin 1,7, angiotensin III, and angiotensin 1,5, and angiotensin-converting enzyme (ACE)-2 activity were higher in SHT/CKD-A cats compared to NT cats, while ACE activity was lower in SHT/CKD-A cats compared to NT cats (p < 0.05 all). A marker for alternative RAAS influence (ALT-S) was significantly higher (69; 58–73 pmol/pmol) in SHT/CKD-A cats compared to NT cats (35; 14–63 pmol/pmol; p = 0.001). Aldosterone concentrations were significantly higher (393; 137–564 pmol/L) in SHT/CKD-A cats compared to NT cats (129; 28–206 pmol/L; p = 0.007). Conclusion and Clinical Importance: Circulating RAAS is activated in systemically hypertensive cats receiving amlodipine. Although this study did not parse out the individual contributions of SHT, chronic kidney disease, and amlodipine, the findings suggest that the use of concurrent RAAS-suppressant therapy, specifically aldosterone antagonism, in amlodipine-treated SHT cats with chronic kidney disease might be indicated.