Prenatal dexamethasone exposure impaired vascular reactivity in adult male offspring cerebral arteries

Background: Cerebrovascular disease is one of the leading causes of death worldwide. Middle cerebral artery (MCA) is the largest and most complex of cerebral arteries. The prenatal period is a critical time for development, which largely determines lifelong health. Clinically, glucocorticoids (GCs) administration to accelerate preterm fetal lung maturation has become standard practice. Prenatal GCs administration increases cardiovascular risks in offspring, but little is known regarding the side effects on offspring MCA function.Objective: We investigated the alterations of MCA reactivity following prenatal GCs administration in postnatal offspring.Method and results: Pregnant Sprague-Dawley rats received synthetic GCs (dexamethasone, DEX) during the last week of pregnancy, and we examined vascular reactivity, cellular electrophysiology, and gene promoter epigenetic modifications in the male offspring MCA. Our results showed that prenatal DEX exposure increased the sensitivity of offspring MCA to Angiotensin II, which was resulted from the increased Cav1.2 (L-type Ca2+ channels subunit alpha1 C). Mechanistically, prenatal DEX exposure resulted in a transcriptionally active chromatin structure at the Cav1.2 gene promoter by altering histone modifications. This activation led to increased expression of vascular Cav1.2 gene, ultimately resulting in increased MCA contractility in offspring.Conclusion: The present study is the first to demonstrate that the adverse effects of prenatal GCs administration on cerebrovascular tone persist into adulthood, providing new insights into developmental origins of cerebrovas-cular disease.

Automated summary

This study demonstrates that prenatal administration of synthetic glucocorticoids (GCs) affects the reactivity of the middle cerebral artery (MCA) in postnatal offspring, increasing their sensitivity to angiotensin II and ultimately leading to increased MCA contractility, which may contribute to the development of cerebrovascular disease.