Intervention against hypertension in the next generation programmed by developmental hypoxia

Area of Science:

• Cardiovascular Physiology
• Developmental Biology
• Obstetrics

Background:

• Adverse pregnancy outcomes are linked to adult cardiovascular disease in offspring.
• Translational studies are needed to identify mechanisms and interventions.
• Sheep models offer relevant cardiovascular developmental parallels to humans.

Purpose of the Study:

• To test if maternal antioxidants (vitamin C) protect against fetal growth restriction and programmed hypertension in sheep exposed to chronic fetal hypoxia.
• To investigate the mechanisms underlying these protective effects.

Main Methods:

• Sheep underwent normoxia or hypoxia (10% O2) with or without maternal vitamin C treatment during the last third of gestation.
• Maternal blood gas status, P50, nitric oxide (NO) bioavailability, oxidative stress, and antioxidant capacity were measured.
• Offspring cardiovascular function and endothelial function were assessed in early adulthood.

Main Results:

• Hypoxic pregnancy caused fetal growth restriction, fetal oxidative stress, adult hypertension, enhanced vasoconstrictor reactivity, and impaired endothelial function.
• Maternal vitamin C improved transplacental oxygenation, enhanced fetal antioxidant capacity, and increased NO bioavailability.
• Vitamin C treatment offset vasoconstrictor hyper-reactivity and restored endothelial function in adult offspring.

Conclusions:

• Maternal vitamin C protects against fetal growth restriction and programmed hypertension in a sheep model of complicated pregnancy.
• This intervention improves NO bioavailability and endothelial function, offering a potential therapeutic strategy.
• Findings provide insight into mechanisms linking adverse pregnancy to offspring cardiovascular disease.