Pregnancy Enhances the Effects of Hypercholesterolemia on Posterior Cerebral Arteries

In preeclampsia, hyperlipidemia is enhanced compared to normal pregnancy that could adversely affect vascular function. In the cerebral vasculature, this could lead to dysregulation of cerebral blood flow and neurological complications. Here, we examined the effect of excessive hyperlipidemia, as seen in preeclampsia, on cerebral artery function and expression of inflammatory markers in pregnancy. Pregnant and nonpregnant rats received a 14-day high-cholesterol diet or normal chow and posterior cerebral artery function was compared. High cholesterol significantly increased sensitivity of posterior cerebral arteries to the nitric oxide donor sodium nitroprusside that was accompanied by a similar to 12-fold increased messenger RNA (mRNA) expression of inducible nitric oxide synthase in late-pregnant rats only. Further, high cholesterol significantly increased peroxynitrite-induced dilation and decreased myogenic tone in cerebral arteries from late pregnant compared to nonpregnant animals. These results suggest that pathologically high levels of cholesterol in pregnancy enhance inflammatory responses and peroxynitrite generation in cerebral arteries.