Loss of the Protective Effect of Estrogen Contributes to Maternal Gestational Hypertension-Induced Hypertensive Response Sensitization Elicited by Postweaning High-Fat Diet in Female Offspring.

Background A recent study conducted in male offspring demonstrated that maternal gestational hypertension (MHT) induces hypertensive response sensitization (HTRS) elicited by postweaning high-fat diet (HFD). In this study, we investigated the sensitizing effect of MHT on postweaning HFD-induced hypertensive response in female rat offspring and assessed the protective role of estrogen in HTRS. Methods and Results The results showed that MHT also induced a sensitized HFD-elicited hypertensive response in intact female offspring. However, compared with male offspring, this MHT-induced HTRS was sex specific in that intact female offspring exhibited an attenuated increase in blood pressure. Ovariectomy significantly enhanced the HFD-induced increase in blood pressure and the pressor response to centrally administered angiotensin II or tumor necrosis factor-α in offspring of normotensive dams, which was accompanied by elevated centrally driven sympathetic activity, upregulated mRNA expression of prohypertensive components, and downregulated expression of antihypertensive components in the hypothalamic paraventricular nucleus. However, when compared with HFD-fed ovariectomized offspring of normotensive dams, the MHT-induced HTRS and pressor responses to centrally administered angiotensin II or tumor necrosis factor-α in HFD-fed intact offspring of MHT dams were not potentiated by ovariectomy, but the blood pressure and elicited pressor responses as well as central sympathetic tone remained higher. Conclusions The results indicate that in adult female offspring MHT induced HTRS elicited by HFD. Estrogen normally plays a protective role in antagonizing HFD prohypertensive effects, and MHT compromises this normal protective action of estrogen by augmenting brain reactivity and centrally driven sympathetic activity.