John B. Pierce Laboratory, New Haven, Connecticut.
Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale School of Medicine , New Haven, Connecticut.
Am J Physiol Heart Circ Physiol. 2018 Oct 1;315(4):H925-H933. doi: 10.1152/ajpheart.00188.2018. Epub 2018 Jun 15.
Hypertension, obesity, and endothelial function predict cardiovascular disease in women, and these factors are interrelated. We hypothesized that hypertension and obesity are associated with endothelial dysfunction in young women and that short-term ethinyl estradiol exposure mitigates this dysfunction. We examined flow-mediated dilation (FMD) responses before and during 7 days of oral ethinyl estradiol (30 µg/day) in 19 women (25 ± 5, 18-35 yr). We divided our sample into two groups based on two criteria: blood pressure and obesity. Women were divided into normal blood pressure (NBP; mean arterial pressure range: 78-91 mmHg, n = 7) and high blood pressure (HBP; mean arterial pressure range: 95-113 mmHg, n = 9) groups. We also stratified our subjects by body composition (lean: 18-31%, n = 8; obese: 38-59%, n = 9). We evaluated brachial FMD after two distinct shear stress stimuli: occlusion alone and occlusion with ischemic handgrip exercise. Obesity was unrelated to both FMD responses. Before ethinyl estradiol administration, the HBP group had blunted ischemic exercise responses relative to the NBP group (8.0 ± 3.5 vs. 12.3 ± 3.2%, respectively, P = 0.05). However, during ethinyl estradiol administration, ischemic exercise responses increased in the HBP group (12.8 ± 6.1%, P = 0.04) but decreased in the NBP group (5.6 ± 2.4%, P = 0.01). Standard FMD did not reveal differences between groups. In summary, 1) moderate HBP predicted endothelial impairment, 2) ethinyl estradiol administration had divergent effects on FMD in women with NBP versus HBP, and 3) enhanced FMD (ischemic handgrip exercise) revealed differences in endothelial function, whereas standard FMD (occlusion alone) did not. NEW & NOTEWORTHY We are the first to show that mild hypertension is a stronger predictor of endothelial dysfunction than obesity in healthy women without overt cardiovascular dysfunction. Importantly, the standard 5-min flow-mediated vasodilation stimulus did not detect endothelial dysfunction in our healthy population; only an enhanced ischemic handgrip exercise shear stress stimulus detected endothelial impairment. Estradiol administration increased flow-mediated dilation in women with high blood pressure, so it may be a therapeutic intervention to improve endothelial function.
高血压、肥胖和内皮功能可预测女性的心血管疾病，且这些因素相互关联。我们假设高血压和肥胖与年轻女性的内皮功能障碍有关，并且短期炔雌醇暴露可减轻这种功能障碍。我们在 19 名女性（25 ± 5 岁，18-35 岁）中检查了口服炔雌醇（30 µg/天）7 天前后的血流介导的扩张（FMD）反应。根据两个标准，我们将样本分为两组：血压和肥胖。女性分为正常血压（NBP；平均动脉压范围：78-91mmHg，n = 7）和高血压（HBP；平均动脉压范围：95-113mmHg，n = 9）组。我们还根据身体成分（瘦：18-31%，n = 8；肥胖：38-59%，n = 9）对我们的受试者进行了分层。我们在两种不同的切变应力刺激后评估了肱动脉 FMD：单独闭塞和闭塞伴缺血性握力运动。肥胖与两种 FMD 反应均无关。在炔雌醇给药之前，HBP 组相对于 NBP 组的缺血性运动反应减弱（分别为 8.0 ± 3.5%和 12.3 ± 3.2%，P = 0.05）。然而，在炔雌醇给药期间，HBP 组的缺血性运动反应增加（12.8 ± 6.1%，P = 0.04），而 NBP 组的反应减少（5.6 ± 2.4%，P = 0.01）。标准 FMD 未显示组间差异。总之，1）中度 HBP 预测内皮损伤，2）炔雌醇给药对 NBP 与 HBP 女性的 FMD 有不同的影响，3）增强的 FMD（缺血性握力运动）揭示了内皮功能的差异，而标准 FMD（单独闭塞）则没有。新的和值得注意的是，我们是第一个表明轻度高血压是健康女性无明显心血管功能障碍的内皮功能障碍的更强预测因子，而不是肥胖。重要的是，我们的健康人群中，标准的 5 分钟血流介导的血管扩张刺激并未检测到内皮功能障碍；只有增强的缺血性握力运动切变应力刺激检测到内皮损伤。雌二醇给药增加了高血压女性的血流介导扩张，因此它可能是改善内皮功能的治疗干预措施。
