Evidence for compromised aldosterone synthase enzyme activity in preeclampsia

Abstract

Aldo deficiency due to a compromised MO step of Aldo synthesis favors extracellular volume depletion, and may account for an increased risk of placental hypoperfusion and consecutive development of preeclampsia. The sole presence of mutation V386A in preeclamptic mothers may identify a subgroup with an increased risk to develop preeclampsia during pregnancy.

Relationship of aldosterone synthase gene (C-344T) and mineralocorticoid receptor (S810L) polymorphisms with gestational hypertension

“…Our work confirms earlier observations stating that plasma aldosterone [5][6][7]26,28 and PRA levels 9,28,29 are lower, and progesterone levels 7 are higher in pregnancy-induced hypertension. Multiple regression analysis shows a negative correlation of both systolic and diastolic blood pressure with aldosterone and PRA, and a positive correlation with progesterone levels.…”

“…In contrast, the second hypothesis focuses on vascular 'underfilling' due to inappropriately low aldosterone levels. 6,31 Although aldosterone levels in pregnancy are controlled by salt intake, we did not measure the urinary sodium excretion or the salt ingestion in our patients, which is rather high in our population, calculated close to 4 g per day. 32 It is important to underline that this is the first study analysing the relationship of the -344C/T polymorphism of the aldosterone synthase CYP11B2 gene with the serum aldosterone concentration in women with gestational hypertension.…”

“…19 In contrast, the genetic polymorphism V386A in exon 7 of CYP11B2 was detected in 17% of preeclamptic women. 6 This polymorphism has been investigated in vitro and has shown to reduce, but not abrogate CYP11B2 activity in cell cultures. 26 Our negative result may be due to the presence of other single nucleotide polymorphisms in CYP11B2 associated with elevated blood pressure and not analysed by us.…”

“…This low plasma volume expansion precedes aldosterone and estradiol diminution. [5][6][7] The renin-angiotensinaldosterone system and estrogens are considered primary modulators of plasma volume expansion during pregnancy. 8 Although plasma aldosterone concentration is reduced in hypertensive pregnant women, the aldosterone-renin ratio is twofold larger than in normal pregnancy, and it may be another manifestation of increased adrenal sensitivity to angiotensin II.…”

“…9 Therefore, one key player in the control of hypertension during pregnancy may be aldosterone synthase (CYP11B2) and the control of CYP11B2 expression may be responsible for hypertension. 6 This single nucleotide polymorphism is located in the CYP11B2 promoter within a putative binding site for the steroidogenic factor-1. Earlier reports have examined the relationship of -344T/C CYP11B2 with essential hypertension in diverse populations, with different results.…”