Blood pressure reduction in pregnancy by sodium chloride

Abstract

Volume expansion in the presence of elevated aldosterone availability is a hallmark of normal pregnancy. Intravascular volume depletion characterizes severe pregnancy-associated disease conditions such as intra-uterine growth retardation, chronic hypertension or pre-eclampsia [1]. Two hypotheses have been forwarded to explain volume depletion in pregnancy: the first hypothesis charges inappropriate sensing of vascular ‘overfilling’, resulting in an increased transendothelial loss of fluid to the extravascular compartment. In contrast, the second hypothesis focuses on vascular ‘underfilling’ due to inappropriately low aldosterone levels. The second hypothesis is based on the assumption that a compensatory increase in the circulating fluid volume is required in normal pregnancy to support fetal substrate delivery. According to the second concept, maternal blood pressure increases due to counter-regulatory mechanisms when placental blood supply is reduced [2]. In support of the ‘underfilling’ hypothesis are observations that a compromised volume status before pregnancy or a reduced ability to retain sodium by pregnant women predicts a complicated pregnancy outcome. The relevance of intravascular volume expansion during normal pregnancy is also supported by the clinical observation that further reduction of fluids by prescribing either diuretics or salt restriction does not prevent or improve the course of the disease [3]. On the contrary, acute volume expansion in overt pre-eclampsia has been observed to transiently decrease blood pressure [4]. Assuming low aldosterone availability to be the cause rather than the consequence of pre-eclampsia [5], we recently observed an association between a reduced 18-methyl oxidase, the rate limiting enzymatic step of aldosterone synthase (CYP11B2), an increased frequency of polymorphisms in the gene of the same enzyme and pre-eclampsia [6]. Likewise, patients with inborn corticosterone methyl oxidase deficiency are known to decompensate at times of sodium deprivation. Here, we demonstrate for the first time the utility of prescribing supplemental NaCl for a woman with neither the increase in aldosterone production nor the blood pressure drop expected during pregnancy.