Department of Psychological and Brain Sciences University of Iowa Iowa City IA.
Department of Internal Medicine University of Iowa Iowa City IA.
J Am Heart Assoc. 2022 Jan 18;11(2):e023685. doi: 10.1161/JAHA.121.023685. Epub 2022 Jan 11.
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.
最近一项针对雄性后代的研究表明，母体妊娠期高血压（MHT）可诱导断奶后高脂肪饮食（HFD）引起的高血压反应敏化（HTRS）。在本研究中，我们调查了 MHT 对断奶后 HFD 诱导的雌性大鼠后代高血压反应的敏化作用，并评估了雌激素在 HTRS 中的保护作用。
结果表明，MHT 也可诱导完整雌性后代对 HFD 引起的高血压反应产生敏化作用。然而，与雄性后代相比，这种 MHT 诱导的 HTRS 具有性别特异性，即完整雌性后代的血压升高幅度减弱。卵巢切除术显著增强了 HFD 诱导的血压升高和中枢给予血管紧张素 II 或肿瘤坏死因子-α引起的升压反应，同时伴有中枢驱动性交感神经活动增加、促高血压成分的 mRNA 表达上调和下丘脑室旁核内降压成分的表达下调。然而，与 HFD 喂养的正常血压母鼠卵巢切除后代相比，MHT 喂养的 MHT 母鼠 HFD 喂养的完整后代的 HTRS 以及对中枢给予血管紧张素 II 或肿瘤坏死因子-α的升压反应并未因卵巢切除术而增强，但血压和引起的升压反应以及中枢交感神经张力仍较高。
这些结果表明，在成年雌性后代中，MHT 可诱导 HFD 引起的 HTRS。雌激素通常在拮抗 HFD 的促高血压作用方面发挥保护作用，而 MHT 通过增强大脑反应性和中枢驱动性交感神经活动来损害雌激素的这种正常保护作用。
