Maternal Apocynin During Experimental Preeclampsia Prevents BBB Permeability and Increased Vascular Tone of Cerebral Arteries in Male but Not Female Rat Adult Offspring.

OBJECTIVE

We examined if exposure to experimental preeclampsia (ePE) impacts vascular permeability and reactivity of posterior cerebral arteries (PCAs) in adult offspring, and if maternal antioxidant treatment prevents these effects in adult male and female offspring.

METHODS

Offspring (F1) from rats with Normal pregnancy (NormPreg_F1), ePE_F1 and ePE treated with apocynin (ePE + apo_F1) were weighed at p24, p31, p38, and p45. Maternal apocynin was administered weekly in drinking water at a dose of ∼24 mg/kg (3 mM) on gestational days 11-20. Blood-brain barrier (BBB) permeability, structure and function of PCAs were measured from male and female adult offspring (n = 8/group, 12-29 weeks). Circulating inflammatory factors were measured by multiplex array.

RESULTS

Male ePE_F1 had smaller body weights than male NormPreg_F1 (p < 0.05) at all ages which was prevented by maternal apocynin. Female ePE_F1 body weights were less only at p24 which was prevented by maternal apocynin. PCAs from male ePE_F1 had increased BBB permeability versus male NormPreg_F1 which was prevented by apocynin (p < 0.05). These changes were not seen in female ePE_F1s. Maternal ePE did not affect PCA reactivity to inward potassium rectifier channel or voltage-operated calcium channel activation, nor reactivity to L-NAME and sodium nitroprusside. There were little differences in plasma inflammatory factors.

CONCLUSIONS

ePE exposure had long-term consequences on the cerebral circulation of adult male offspring. Understanding the underlying mechanism by which PE adversely impacts the brain of offspring may lead to the prevention of cognitive decline and stroke in adulthood.