Abstract TP431: Role of Aromatase in Cerebrovascular Endothelial Function in Female Mice
Women are at lower risk for stroke than age-matched men even after menopause when ovarian estrogen is lost and the major source of estrogen becomes local (extra-gonadal) synthesis by the enzyme aromatase. Aromatase gene deletion in ovariectomized female mice exacerbates ischemic brain damage after stroke. It is not clear however which cell type is responsible for this effect, since aromatase is expressed in multiple cell types in brain, including cerebrovascular endothelium. Therefore, we tested the hypothesis that endothelial aromatase plays an important role in endothelium-dependent cerebrovascular function in females, which in part contributes to the sex difference in endothelial function in the cerebral microcirculation. Cerebrocortical microvascular responses to the endothelium-dependent vasodilator acetylcholine (ACh; 1-100 μM) were compared between male and female wild-type (WT) and aromatase knockout (ArKO) mice using an in-vivo closed cranial window preparation combined with laser Doppler perfusion monitoring. WT female mice had significantly greater response to ACh at doses between 10-100 μM (10 μM = 267 +/- 41%, 100 μM= 273 +/- 51%) compared to both WT male (10 μM = 144 +/- 19%, 100 μM= 156 +/- 19%) and ArKO female mice (10 μM= 158 +/- 21%, 100μM = 165 +/- 22%) (mean +/- SEM, *p<0.01, ANOVA). We conclude that aromatase plays an important role in endothelium-dependent vascular responses in female cerebral vessels, which may contribute to the observed sex differences in cerebrovascular function and response to ischemic injury.
- © 2012 by American Heart Association, Inc.