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 chisquare tests, and linear regression controlling for age. Data are expressed as median (minimum, maximum) and P < .05 was considered significant.

The effect of taurine supplementation on the renin–angiotensin–aldosterone system of dogs with congestive heart failure

“…Consistent with previous studies of the known ACE variant in dogs, we found that ACE activity was significantly lower in ACE gene variant positive dogs compared to ACE gene wildtype dogs 31 . The lack of difference in ACE-S (a proposed surrogate for ACE activity) between ACE variant and wildtype dogs has also been previously reported 32 , 33 . Because ACE-S is simply the ratio of angiotensin II to angiotensin I, it appears not to reflect true ACE activity in dogs with the ACE variant because other non-ACE enzymes (e.g.…”

“…The activity of ACE2 has not been previous reported in dogs with CHF. The ACE2 activity for this group of CHF dogs was notably higher than reported for both healthy people and people with CHF 34 but was not markedly different from healthy dogs 33 . This enzyme is a marker for disease severity in people with heart disease.…”

“…Analyte concentrations were reported in pmol/L and the lower limit of quantification was reported for each metabolite. The activities of ACE and ACE2 were measured with a kinetics approach using spiked substrate 33 , 36 . Activity of ACE was determined by measuring the formation of angiotensin II after addition of angiotensin I in the presence and absence of an ACE inhibitor and a chymase inhibitor to determine the ACE-inhibitor sensitive fraction of angiotensin II generation.…”

“…The ratio of aldosterone to angiotensin II (AA2) was calculated as a unitless indicator of adrenal responsiveness to angiotensin II stimulation of aldosterone release 32 . The sum of angiotensins 1–7 and 1–5 divided by the sum of angiotensins I, II, 1–7, and 1–5, was calculated as a unitless marker of renin-independent alternative RAAS activation (ALT-S) 33 . The ratio of angiotensin 1–7/angiotensin I was calculated to account for overall RAAS activity to aid interpretation of the balance of angiotensin 1–7 formation and breakdown 33 .…”