Increased salt sensitivity in offspring of pregnancies complicated by experimental preeclampsia

Abstract

Preeclampsia is a hypertensive disorder of pregnancy known to increase the risk of cardiovascular disease in mothers and offspring. Offspring exposed to a suboptimal intrauterine environment may experience altered fetal programming and subsequent long-term cardiovascular changes. This study investigated changes in the vascular response in offspring from experimental preeclampsia (EPE) induced by uterine artery ligation, in the absence of fetal growth restriction, compared to normal baboon pregnancies (controls), following a high salt diet challenge. After 1 week of standard diet (containing <1% salt), animals were fed a high salt diet (6%) for 2 weeks. Systolic and diastolic blood pressure (SBP, DBP), aldosterone, renin and creatinine clearance were evaluated in EPE (n = 6, 50% male) and control (n = 6, 50% male) offspring. A repeated measures analysis was performed, and P < 0.05 was considered significant. At baseline, there were no differences between the groups in any parameter (EPE, mean age and weight 3.2 ± 1.2 years, 6.8 ± 1.0 kg, respectively; Control, 2.9 ± 0.8 years, 7.1 ± 1.5 kg). After salt loading the EPE group had significantly higher SBP (92 ± 5 mm Hg) compared to the control group (83 ± 4 mm Hg, P = 0.03). Aldosterone concentration was higher in the EPE group despite the same salt excretion and no difference in renal function. Salt sensitivity may differ in offspring from hypertensive pregnancies due to fetal programming. This could have long-term consequences for cardiovascular health of EPE offspring and further research is required to determine the exact pathological mechanisms.

Paternal diet impairs F1 and F2 offspring vascular function through sperm and seminal plasma specific mechanisms in mice

“…; Yeung et al . ). Recently, studies have begun to define the association between poor paternal diet and offspring cardiovascular health (Bromfield et al .…”

“…A second key observation was that poor paternal diet altered adult offspring vascular function. Significant impairments in offspring vasoconstriction and vasodilatory responses have been observed in multiple models of developmental programming (Watkins et al 2010;Loche et al 2018;Yeung et al 2018). Recently, studies have begun to define the association between poor paternal diet and offspring cardiovascular health (Bromfield et al 2014;McPherson et al 2016).…”

Short- and Long-Term Outcomes of Preeclampsia in Offspring: Review of the Literature

“…Finally, fetal programming in the offspring of hypertensive mothers may also affect salt sensitivity. A study investigating the different vascular responses of the offspring exposed to experimental late-onset preeclampsia (EPE) found increased aldosterone concentrations in the EPE group with no differences in salt excretion and renal function [124].…”

Mechanisms linking exposure to preeclampsia in utero and the risk for cardiovascular disease

“…For example, the switch from cardiomyocyte proliferation to hypertrophy occurs postnatally in rodents but before birth in other species including humans. 64 A recent report that progeny of preeclamptic baboons exhibit elevated systolic blood pressure during a dietary salt loading challenge 65 provides direct evidence of cardiovascular programming by in utero exposure to PE in species that are more mature at birth, although studies with greater animal numbers are needed to assess any sex differences.…”