Plasma from preeclamptic women increases blood-brain barrier permeability: role of vascular endothelial growth factor signaling.

Circulating factors in preeclamptic women are thought to cause endothelial dysfunction and thereby contribute to the progression of this hypertensive condition. Despite the involvement of neurological complications in preeclampsia, there is a paucity of data regarding the effect of circulating factors on cerebrovascular function. Using a rat model of pregnancy, we investigated blood-brain barrier permeability, myogenic activity, and the influence of endothelial vasodilator mechanisms in cerebral vessels exposed intraluminally to plasma from normal pregnant or preeclamptic women. In addition, the role of vascular endothelial growth factor signaling in mediating changes in permeability in response to plasma was investigated. A 3-hour exposure to 20% normal pregnant or preeclamptic plasma increased blood-brain barrier permeability by ≈6.5- and 18.0-fold, respectively, compared with no plasma exposure (P<0.01). Inhibition of vascular endothelial growth factor receptor kinase activity prevented the increase in permeability in response to preeclamptic plasma but had no effect on changes in permeability of vessels exposed to normal pregnant plasma. Circulating factors in preeclamptic plasma did not affect myogenic activity or the influence of endothelium on vascular tone. These findings demonstrate that acute exposure to preeclamptic plasma has little effect on reactivity of cerebral arteries but significantly increases blood-brain barrier permeability. Prevention of increased permeability by inhibition of vascular endothelial growth factor signaling suggests that activation of this pathway may be responsible for increased blood-brain barrier permeability after exposure to preeclamptic plasma.

Resistance artery adaptation to pregnancy counteracts the vasoconstricting influence of plasma from normal pregnant women.

Using a rat model, we investigated the effects of circulating factors in pregnancy on cerebrovascular and systemic vascular function by comparing myogenic reactivity, tone, and endothelial vasodilator production of the posterior cerebral artery (PCA) and mesenteric artery (MA) of nonpregnant (NP) animals perfused with nonpregnant and pregnant human plasma. Arteries from late pregnant (LP) animals were then perfused similarly to evaluate a potential adaptive effect of pregnancy on vessel function. A 3-hour exposure to pregnant plasma caused increased myogenic reactivity and tone in vessels from NP animals and produced a decreased endothelium-derived hyperpolarizing factor response in NP PCAs, findings that were not seen with MAs. The increased reactivity and tone noted in NP vessels was abolished when pregnant plasma was perfused through LP arteries, suggesting these vessels adapt during pregnancy to the vasoconstricting influence of pregnant plasma.

Maternal hemoglobin concentration and its association with birth weight in newborns of mothers with preeclampsia.

OBJECTIVE: Maternal hemoglobin concentration is inversely related to newborn size presumably through plasma volume constriction. We sought to determine whether birth weight would show an inverse relationship to hemoglobin concentration in a group of infants whose mothers had preeclampsia, where plasma volume constriction is common. METHODS: Electronic and paper chart review identified 142 nulliparous women with preeclampsia (excluding hemolysis, elevated liver enzymes, low platelets syndrome). Birth weight percentile was determined based on cross-sectional hybrid growth curves. Maximal third trimester maternal hemoglobin concentrations were obtained and standardised to z-scores based on gestational age matched normative data. Birth weight percentile was examined as a function of hemoglobin z-score using appropriate statistics. RESULTS: Average gestational age at delivery was 35.9 +/- 1.9 weeks. Mean birth weight percentile for infants of preeclamptic mothers was 34 +/- 32. Mean hemoglobin z-score for mothers with preeclampsia was 0.3 +/- 1.5, significantly higher than a control population (p = 0.04). Maternal hemoglobin z-score was inversely associated with birth weight percentile (r = -0.18, p = 0.03). CONCLUSION: Maternal hemoglobin concentrations are significantly elevated prior to delivery in women with preeclampsia. There is a statistically significant inverse correlation of maternal hemoglobin concentration to birth weight percentile.