Treatment with apocynin selectively restores hippocampal arteriole function and seizure-induced hyperemia in a model of preeclampsia

Abstract

Preeclampsia (PE) is a hypertensive disorder of pregnancy associated with neurovascular dysfunction, cognitive impairment and increased seizure susceptibility. Here, we sought to determine if treatment of experimental PE (ePE) rats with apocynin could prevent hippocampal arteriolar (HA) dysfunction and impaired seizure-induced hyperemia within the hippocampus, a brain region central to cognition and seizure generation. Isolated and pressurized HAs from Sprague Dawley rats that were normal pregnant (Preg; n = 8), ePE (n = 8) or ePE treated with apocynin for 2 weeks of gestation (ePE + apo; n = 8) were compared. Hippocampal blood flow (n = 6/group) was measured using hydrogen clearance before and during seizure. Aorta elastin was quantified using histochemistry. ePE was associated with HA dysfunction including reduced contraction to endothelin-1 and diminished dilation to the endothelium-dependent vasodilator NS309 that was prevented by apocynin. However, apocynin had no effect on ePE-induced impairment of dilation to the nitric oxide donor sodium nitroprusside, but increased myogenic tone and substantially increased HA distensibility. Seizure-induced hyperemia was impaired in ePE rats that was restored by apocynin. Aorta from ePE rats had reduced elastin content, suggesting large artery stiffness, that was unaffected by apocynin. Thus, while apocynin partially prevented HA dysfunction, its restoration of functional hyperemia may be protective of seizure-induced injury during eclampsia.