Prenatal dexamethasone programs autonomic dysregulation in female rats

Area of Science:

• Cardiovascular Physiology
• Neuroendocrinology
• Autonomic Nervous System

Background:

• Autonomic dysfunction is linked to cardiovascular and neurological disorders.
• Prenatal exposure to glucocorticoids like dexamethasone (DEX) may program autonomic dysfunction.
• Previous studies show DEX exposure increases stress-responsive cardiovascular measures in female offspring.

Purpose of the Study:

• To investigate the impact of sympathetic (SYM) or parasympathetic (PS) blockade on cardiovascular function in male and female rat offspring exposed to maternal DEX in utero.
• To assess stress-responsive cardiovascular function and autonomic balance following prenatal DEX exposure.

Main Methods:

• Rat offspring of mothers injected with DEX or vehicle during late gestation (GD 18-21) were studied at 11-12 weeks of age.
• Mean arterial pressure (MAP), heart rate (HR), and heart rate variability (HRV) were measured at baseline and after SYM blockade, PS blockade, or saline.
• Restraint stress was applied to assess stress-responsive function; tyrosine hydroxylase, β1 adrenergic receptor, choline acetyltransferase, and acetylcholinesterase were quantified.

Main Results:

• Maternal DEX exposure reduced basal HRV in both male and female offspring.
• PS blockade exacerbated stress-responsive MAP and HR in DEX-exposed females compared to controls.
• SYM and PS blockade had equivalent effects on HR and MAP responses in males, irrespective of maternal treatment.

Conclusions:

• Maternal DEX injection in late gestation disrupts autonomic regulation of cardiovascular function, particularly in females.
• This disruption results in a shift towards increased sympathetic and decreased parasympathetic input in female offspring.
• Prenatal DEX exposure alters sympathovagal balance, potentially mediated by central autonomic circuitry changes.