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.

Keywords: ACE; Doberman Pinscher; RAAS; estrogen; genotype.