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.

中文翻译：

---

血管紧张素转换酶基因多态性犬血管紧张素转换酶抑制剂给药前后的肾素-血管紧张素醛固酮谱。

背景技术血管紧张素转换酶（ACE）基因多态性发生在狗中。但是，对功能重要性的研究还不够深入。假设我们假设，具有多态性的狗与没有多态性的狗相比，只有在ACE-后才显示这种模式的狗会显示出替代性的肾素-血管紧张素醛固酮系统（RAAS）途径激活和经典的RAAS途径抑制。抑制剂管理。动物21只患有二尖瓣疾病的狗因ACE基因多态性而进行了基因分型。方法这项回顾性研究使用了依那普利给药前后8只ACE基因多态性阴性（PN）狗和13只ACE基因多态性阳性（PP）狗的储存样品。进行平衡分析以评估血清RAAS代谢产物和酶活性。在依那普利之前和之后以及各组之间比较结果。结果依那普利给药后两种基因型的经典RAAS途径均被抑制，替代RAAS途径得到增强，而依那普利给药前无差异。尽管抑制了血管紧张素II，但在PN（38％）和PP（54％）的狗中都发生了醛固酮突破。依那普利治疗后，ACE基因PP狗（中位数为92.17 pM； IQR，21.85-184.70）中的醛固酮水平显着高于ACE基因PN狗（中位数为15.91 pM； IQR，<15.00-33.92）。结论和临床意义ACE基因多态性并未改变基线RAAS活性。某些狗的醛固酮通透提示，非血管紧张素介导的醛固酮生成可能受到基因型的负面影响。当对犬，尤其是对ACE基因多态性呈阳性的狗指示RAAS抑制时，这些结果支持醛固酮受体拮抗剂与ACE抑制剂一起使用。