Fetal Undernutrition Modifies Vascular RAS Balance Enhancing Oxidative Damage and Contributing to Remodeling

Area of Science:

• Cardiovascular Physiology
• Developmental Biology
• Endocrinology

Background:

• Fetal programming links early-life stress to adult cardiometabolic diseases and hypertension.
• The renin-angiotensin system (RAS), oxidative damage, and vascular remodeling are implicated in this process.

Purpose of the Study:

• To investigate the relationship between vascular RAS, oxidative damage, and mesenteric artery remodeling in fetal programming induced by maternal undernutrition.
• To assess the impact of maternal undernutrition on blood pressure and vascular structure in offspring.

Main Methods:

• Used Sprague-Dawley rats with maternal undernutrition (50% intake) during the second half of gestation.
• Analyzed mesenteric artery expression of RAS components (ACE, ACE2, AT1, AT2, Mas, MrgD receptors) and NADPH oxidase via qPCR and immunohistochemistry.
• Measured plasma carbonyls (oxidative stress marker) and blood pressure.

Main Results:

• Maternal undernutrition upregulated ACE, ACE2, AT1 receptors, and NADPH oxidase, while downregulating AT2, Mas, and MrgD receptors in offspring mesenteric arteries.
• Offspring exhibited higher systolic/diastolic blood pressure and plasma carbonyl levels.
• Vascular remodeling included increased media/lumen and adventitia/lumen ratios and more connective tissue.

Conclusions:

• Fetal undernutrition alters the vascular RAS and increases oxidative damage.
• These changes contribute to mesenteric artery remodeling and elevate the risk of hypertension and adverse cardiovascular events in offspring.