Key result
After enalapril administration, aldosterone levels were significantly higher in ACE gene polymorphism-positive dogs (median 92.17 pM) compared to negative dogs (median 15.91 pM; P=0.02).
Why the study?
An angiotensin-converting enzyme gene polymorphism occurs in dogs, but its functional importance is not well studied.
Does ACE gene polymorphism affect RAAS pathway activation before and after enalapril administration in dogs with mitral valve disease?
Observational (n=21)
Does ACE gene polymorphism affect RAAS pathway activation before and after enalapril administration in dogs with mitral valve disease?
ACE gene polymorphism in dogs with mitral valve disease is associated with higher aldosterone levels after enalapril treatment, supporting the addition of aldosterone receptor antagonists.
No baseline RAAS difference by ACE genotype; higher post-enalapril aldosterone in positives supports MRA addition with ACEi, though prospective validation required.
BACKGROUND: An angiotensin-converting enzyme (ACE) gene polymorphism occurs in dogs; however, functional importance is not well studied. HYPOTHESIS: We hypothesized that dogs with the polymorphism would show alternative renin-angiotensin aldosterone system (RAAS) pathway activation and classical RAAS pathway suppression before and after ACE-inhibitor administration, as compared to dogs without the polymorphism that would show this pattern only after ACE-inhibitor administration. ANIMALS: Twenty-one dogs with mitral valve disease that were genotyped for the ACE gene polymorphism. METHODS: This retrospective study utilized stored samples from 8 ACE gene polymorphism-negative (PN) dogs and 13 ACE gene polymorphism-positive (PP) dogs before and after enalapril administration. Equilibrium analysis was performed to evaluate serum RAAS metabolites and enzyme activities. Results were compared before and after enalapril, and between groups. RESULTS: The classical RAAS pathway was suppressed and the alternative RAAS pathway was enhanced for both genotypes after administration of enalapril, with no differences before enalapril administration. Aldosterone breakthrough occurred in both PN (38%) and PP (54%) dogs despite angiotensin II suppression. Aldosterone was significantly higher (P = .02) in ACE gene PP dogs (median, 92.17 pM; IQR, 21.85-184.70) compared to ACE gene PN dogs (median, 15.91 pM; IQR, <15.00-33.92) after enalapril. CONCLUSIONS AND CLINICAL IMPORTANCE: The ACE gene polymorphism did not alter baseline RAAS activity. Aldosterone breatkthrough in some dogs suggests nonangiotensin mediated aldosterone production that might be negatively influenced by genotype. These results support the use of aldosterone receptor antagonists with ACE-inhibitors when RAAS inhibition is indicated for dogs, especially those positive for the ACE gene polymorphism.
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Adin et al. (2020) conducted an observational in mitral valve disease (n=21). ACE gene polymorphism vs. ACE gene polymorphism-negative was evaluated on Aldosterone level after enalapril administration (p=0.02). After enalapril administration, aldosterone levels were significantly higher in ACE gene polymorphism-positive dogs (median 92.17 pM) compared to negative dogs (median 15.91 pM; P=0.02).
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