Department of Pharmacy, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 833, Taiwan.
Department of Obstetrics and Gynecology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 833, Taiwan.
Int J Mol Sci. 2019 Sep 6;20(18):4382. doi: 10.3390/ijms20184382.
Maternal exposure to endocrine disrupting chemicals (EDCs) and a high-fat intake may induce the developmental programming of hypertension in adult offspring. Bisphenol A (BPA) is one of the most commonly environmental EDCs. As the nitric oxide (NO) and aryl hydrocarbon receptor (AHR) signaling pathways both contribute to the pathogenesis of hypertension, we evaluated whether resveratrol, an antioxidant and an AHR antagonist, can prevent hypertension programmed by a maternal BPA and HF diet. Sixteen-week-old male rat offspring were assigned to six groups (n = 8 per group): Control, HF (D12331, Research Diets), BPA (50 μg/kg/day), HF + BPA, BPA + R (resveratrol 50mg/L in drinking water throughout pregnancy and lactation), and HF + BPA + R. Maternal BPA exposure exacerbated hypertension programmed by HF consumption in adult male offspring, which was protected by maternal resveratrol therapy. The BPA and HF diet synergistically induced oxidative stress in offspring kidneys, which resveratrol treatment prevented. We observed that HF + BPA-induced programmed hypertension was associated with a decreased NO bioavailability, increased oxidative stress, and an activated AHR signaling pathway. The beneficial effects of resveratrol are relevant to restoring NO bioavailability, reducing oxidative stress, and antagonizing the AHR signaling pathway. Our results cast a new light on resveratrol as a reprogramming strategy to protect against hypertension programmed by combined BPA and HF exposure, but this strategy has yet to be translated into clinical applications.
母体暴露于内分泌干扰化学物质（EDCs）和高脂肪饮食可能导致成年后代高血压的发育编程。双酚 A（BPA）是最常见的环境 EDC 之一。由于一氧化氮（NO）和芳香烃受体（AHR）信号通路都有助于高血压的发病机制，我们评估了白藜芦醇（一种抗氧化剂和 AHR 拮抗剂）是否可以预防母体 BPA 和 HF 饮食引起的高血压。16 周龄雄性大鼠后代被分为六组（每组 n = 8）：对照组、HF（D12331，Research Diets）、BPA（50μg/kg/天）、HF+BPA、BPA+R（白藜芦醇 50mg/L 饮用水贯穿妊娠和哺乳期）和 HF+BPA+R。母体 BPA 暴露加剧了 HF 消耗引起的成年雄性后代高血压，而母体白藜芦醇治疗则保护了这种高血压。BPA 和 HF 饮食协同诱导后代肾脏氧化应激，而白藜芦醇治疗则预防了这种应激。我们观察到，HF+BPA 诱导的程序性高血压与 NO 生物利用度降低、氧化应激增加和 AHR 信号通路激活有关。白藜芦醇的有益作用与恢复 NO 生物利用度、减少氧化应激和拮抗 AHR 信号通路有关。我们的研究结果为白藜芦醇作为一种重编程策略提供了新的思路，可预防 BPA 和 HF 联合暴露引起的高血压，但该策略尚未转化为临床应用。
