Role of fetal nutrient restriction and postnatal catch‐up growth on structural and mechanical alterations of rat aorta

Abstract

Fetal undernutrition programmes hypertension development, males being more susceptible. Deficient fetal elastogenesis and vascular growth is a possible mechanism. We investigated the role of aortic mechanical alterations in a rat model of hypertension programming, evaluating changes at birth, weaning and adulthood. Dams were fed ad libitum (Control) or 50% of control intake during the second half of gestation (maternal undernutrition, MUN). Offspring aged 3 days, 21 days and 6 months were studied. Blood pressure was evaluated in vivo. In the thoracic aorta we assessed gross structure, mechanical properties (intact and purified elastin), collagen and elastin content and internal elastic lamina (IEL) organization. Only adult MUN males developed hypertension (systolic blood pressure: MUN = 176.6 ± 5.6 mmHg; Control = 136.1 ± 4.9 mmHg). At birth MUN rats were lighter, with smaller aortic cross-sectional area (MUN = (1.51 ± 0.08) × 10 μm , Control = (2.8 ± 0.04) × 10 μm ); during lactation MUN males and females exhibited catch-up growth and aortic hypertrophy (MUN = (14.5 ± 0.5) × 10 μm , Control = (10.4 ± 0.9) × 10 μm ), maintained until adulthood. MUN aortas were more compliant until weaning (functional stiffness: MUN = 1.0 ± 0.04; Control = 1.3 ± 0.03), containing less collagen with larger IEL fenestrae, returning to normal in adulthood. Purified elastin from young MUN offspring was more compliant in both sexes; only MUN adult females maintained larger elastin compliance (slope: MUN = 24.1 ± 1.9; Control = 33.3 ± 2.8). Fetal undernutrition induces deficient aortic development followed by hypertrophic remodelling and larger aortic compliance in the perinatal period, with similar alterations in collagen and elastin in both sexes. The observed alterations argue against an initial mechanical cause for sex differences in hypertension development. However, the maintenance of high elastin compliance in adult females might protect them against blood pressure rise.

Fetal Undernutrition Induces Resistance Artery Remodeling and Stiffness in Male and Female Rats Independent of Hypertension

“…The diastolic and systolic blood pressure (DBP, SBP; mm Hg) and heart rate (HR; beats/min) were analyzed. Quantification was performed averaging the data in the pressure wave trace for approximately 1 min during the last part of the recording period [ 8 ].…”

“…Males seem to be more susceptible to adverse fetal environments than females, and the majority of studies, including ours, evidence that female rats do not develop hypertension or develop milder forms in adult age [ 2 , 8 , 16 , 17 ]. Based on these data, the impact of adverse intrauterine environments on females is not completely accepted and is sometimes neglected.…”

“…However, the role of vascular remodeling in hypertension induced by fetal programming remains controversial [ 3 ]. In aorta from one-month-old rats exposed to fetal undernutrition, we have reported increased wall thickness, but better compliance, and in adult age, no alterations in mechanical behavior were detected [ 8 ]. In addition to elastic artery stiffening, resistance artery narrowing and subsequent increase in total peripheral resistance is another key mechanism associated with hypertension [ 9 , 10 ].…”

Challenges and controversies in perinatal physiology

“…show in rats that maternal nutrient reduction leading to intrauterine growth restriction (IUGR) is associated with structural and mechanical alterations of the aorta followed by hypertrophic remodelling and larger aortic compliance in the perinatal period (Gutierrez‐Arzapalo et al . ). These changes are strikingly specific to males.…”

A tough life in utero doesn't necessarily make for a stiff future: sex matters for aortic passive mechanics

“…The study by Gutiérrez‐Arzapalo et al . () in this issue of The Journal of Physiology explored if the sex‐dependent manifestation of hypertension is underpinned by differences in the passive mechanical wall properties of the aorta. In an elegant study that pushed the boundaries in the DoHAD field in terms of methods used to explore the nature of the extracellular matrix, the authors revealed structural immaturity of the aortic wall that manifested as reduced stiffness in young offspring of both sexes.…”