Abstract 067: Suppression Of The Renin Angiotensin Aldosterone System In Human Hypertensive Pregnancy

Abstract

In healthy pregnancy, elevated renin activity stimulates aldosterone release via angiotensin II (Ang II) signaling. Despite the known importance in blood volume expansion, mechanisms of aldosterone secretion during pregnancy are not well understood. In vitro / in vivo evidence that aldosterone concentrations are disproportionally elevated compared to renin activity suggest altered sensitivity to Ang II or nonangiotensin stimulation during pregnancy. We used a novel LC-MS/MS-based methodology to quantify serum biomarkers of the renin-angiotensin-aldosterone system (RAAS) in order to evaluate renin-aldosterone relationships in healthy and hypertensive human pregnancy. We recruited 73 pregnant individuals with no known hypertension and followed them prospectively for the development of gestational hypertension or pre-eclampsia outcomes (HYP, n=27), no adverse outcomes (No AO, n=27), or adverse outcomes that were non-hypertensive (AO, Non-HYP, n=20). Concentrations of Ang peptides I and II and aldosterone were quantified from first and third trimester serum. Blood pressure was elevated starting in the first trimester in women who developed HYP outcomes (P<0.01). Renin activity (calculated by [Ang I + Ang II]) and aldosterone concentrations significantly increased from first to third trimester in No AO and AO Non-HYP (renin activity, 30% and 37% increase; aldosterone, 230% and 238% increase, respectively, P<0.001). This was in contrast to HYP pregnancies, where renin activity and aldosterone increased by 19% and 70%, respectively, and were not significant(P=0.54). Further, third trimester aldosterone was significantly lower, median (interquartile range) = 492 (260 - 827) pmol/L compared to No AO = 828 (467-1778) and AO Non-HYP = 1046 (527 - 1368) pmol/L (P<0.01). There was a significant increase in the aldosterone to Ang II ratio over gestation in No AO and AO Non-HYP pregnancies(P<0.01), but not HYP. Taken together, we propose that activity of the RAAS is suppressed in pregnancies that develop hypertension, likely a compensatory response to already-elevated BP. Further, non-hypertensive pregnancy is characterized by a preferential increase in aldosterone, where mechanisms may be impaired in pregnancies that develop hypertension.