Influence of sex on renin‐angiotensin‐aldosterone system metabolites and enzymes in Doberman Pinschers

Abstract Background Estrogen modulates the renin‐angiotensin‐aldosterone system (RAAS) in women, but sex differences have not been fully explored in dogs. Objective We hypothesized that the RAAS profile of intact female (IF) Doberman Pinschers (DP) would differ from spayed female (SF) and intact male (IM) DP. Animals Eighteen healthy DP (6 IF, 6 SF, 6 IM). Methods Absolute and indexed RAAS metabolites, angiotensin‐converting enzyme (ACE) and ACE2 activities, and genotypes (pyruvate kinase dehydrogenase 4, titin, and ACE variants) were compared among sex groups using Kruskal‐Wallis or chi‐square tests, and linear regression controlling for age. Data are expressed as median (minimum, maximum) and P < .05 was considered significant. Results The ACE activity was higher in IF DP (656 pmol/L; 436, 784) compared to SF DP (411 pmol/L; 287, 451; P = .01) and IM DP (365 pmol/L; 276, 1200; P = .04) after controlling for age. Angiotensin II, angiotensin I, and plasma renin activity marker (PRA‐S) were higher in IF DP compared to SF DP, but not significantly (P ≤ .25). After controlling for age, angiotensin 1‐7/angiotensin I was lower in IF DP compared to SF DP (P = .01). Genotypes did not differ among groups. Most DP (94%) were ACE variant positive. Conclusions and Clinical Significance Sex and reproductive status influenced the RAAS of DP, with IF DP showing genotype‐independent higher ACE activity. These findings hold implications for sterilization practices in female dogs, and support sex and reproductive status as a source of variability in RAAS studies. Additionally, the frequency of the ACE gene variant was very high in this group of DP.