Activation of the Renin–Angiotensin–Aldosterone System Is Attenuated in Hypertensive Compared with Normotensive Pregnancy

Abstract

Hypertension during pregnancy increases the risk of adverse maternal and fetal outcomes, but the mechanisms of pregnancy hypertension are not precisely understood. Elevated plasma renin activity and aldosterone concentrations play an important role in the normal physiologic adaptation to pregnancy. These effectors are reduced in patients with pregnancy hypertension, creating an opportunity to define the features of the renin–angiotensin–aldosterone system (RAAS) that are characteristic of this disorder. In the current study, we used a novel LC-MS/MS-based methodology to develop comprehensive profiles of RAAS peptides and effectors over gestation in a cohort of 74 pregnant women followed prospectively for the development of gestational hypertension and pre-eclampsia (HYP, 27 patients) versus those remaining normotensive (NT, 47 patients). In NT pregnancy, the plasma renin activity surrogate, (PRA-S, calculated from the sum of Angiotensin I + Angiotensin II) and aldosterone concentrations significantly increased from the first to the third trimester, accompanied by a modest increase in the concentrations of angiotensin peptide metabolites. In contrast, in HYP pregnancies, PRA-S and angiotensin peptides were largely unchanged over gestation, and third-trimester aldosterone concentrations were significantly lower compared with those in NT pregnancies. The results indicated that the predominant features of pregnancies that develop HYP are stalled or waning activation of the RAAS in the second half of pregnancy (accompanied by unchanging levels of angiotensin peptides) and the attenuated secretion of aldosterone.

Circulating angiotensin-(1–7) is decreased in patients with isolated nocturnal hypertension

“…Surprisingly, Ang II levels were also lower in INHT when compared with the normotensive group. In accord with our results, an attenuation in Ang-(1-7) and Ang II levels in hypertensive compared with normotensive pregnancy has been recently reported [6].…”

Hypertension Related Co-Morbidities and Complications in Women of Sub-Saharan Africa: A Brief Review

“…166 An HDP study shows the upregulation of proinflammatory cytokines (TNFα [tumor necrosis factor alpha], IL-1B [interleukin-1 beta], and INFy [interferongamma]), revealing that cytokine inhibitors or blockers could contribute to decreasing the severity of HDP. 167,168 Family history and DNA methylation at specific sites (cytosine nucleotides followed by guanine nucleotide in 5'→3' direction 43 and cytosine nucleotides followed by guanine nucleotide in 5'→3' direction 26) play roles in HDP. Specifically, DNA methylation at cytosine nucleotides followed by guanine nucleotide in 5'→3' direction 26 may play a role in the development of preeclampsia.…”

Association of Elevated Serum Aldosterone Concentrations in Pregnancy with Hypertension

“…Quantification of angiotensin I, angiotensin II, and aldosterone from serum samples of study patients was performed using LC-MS/MS-based methodology that has been previously described [17,24,25]. Serum samples were incubated for one hour at 37 • C to generate a controlled ex vivo equilibration, followed by stabilization through addition of an enzyme inhibitor cocktail (i.e., equilibrium analysis).…”

“…In a healthy pregnancy, plasma renin activity and aldosterone concentrations increase to accommodate blood volume expansion and the development of the placental-fetal unit [12,13]. Previous studies by our lab and others have reported that gestational hypertension and/or pre-eclampsia is accompanied by attenuated renin activity and lower aldosterone concentrations compared to normotensive pregnancies [14][15][16][17], presumably reflecting a response to increased systemic vascular resistance. Few studies have investigated the condition of aldosterone excess in pregnancy; the literature comprises only a handful of retrospective studies and case reports of pregnant patients with confirmed aldosteronism.…”

“…To being to address these gaps, we used a previously described [17], liquid chromatography with tandem mass spectrometry (LC-MS/MS)-based method to quantify angiotensin peptides and aldosterone concentrations in serum in a cohort of pregnant women followed prospectively for the development of HDP (remaining normotensive, chronic hypertension, gestational hypertension, pre-eclampsia, superimposed pre-eclampsia on chronic hypertension). The aims of our study were to define associations among aldosterone concentrations in serum with blood pressure and hypertension outcomes in pregnancy, and to characterize activity of the RAAS in those with the highest levels of aldosterone.…”