Richey Rauchelle E, Miner Jennifer A, Miner Jonathon C, Brunt Vienna E, Kaplan Paul F, Halliwill John R, Minson Christopher T
Department of Human Physiology, University of Oregon, Eugene, Oregon, United States.
Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Oregon Health Sciences University, Portland, Oregon, United States.
Am J Physiol Heart Circ Physiol. 2025 Aug 1;329(2):H439-H449. doi: 10.1152/ajpheart.00131.2025. Epub 2025 Jul 3.
Women have a greater reduction in cardiovagal baroreflex sensitivity (CVBRS) as they age which contributes to an elevated cardiovascular disease risk. One potential contributor to the attenuated CVBRS may be reductions in estrogen. Therefore, we tested the hypothesis that isolated estradiol (E) and combined E and progesterone (P) would increase CVBRS to the same extent. To examine the acute effects of E and P on CVBRS in healthy premenopausal women, we used a gonadotropin-releasing hormone antagonist to suppress endogenous sex hormones. We tested 29 young adult women over 10-12 days of hormone manipulation. After 4 days of hormone suppression, participants were given either 0.1-0.2 mg transdermal estradiol (E) or 200 mg oral micronized progesterone (P) per day. Following 3-4 days of isolated hormones, combined hormones (200 mg of progesterone and 0.1-0.2 mg estradiol) were administered. CVBRS was assessed during a modified Oxford protocol approximately 4 days following each change in hormones. Overall CVBRS was determined as the slope of the response between the R-R interval and systolic blood pressure. CVBRS slope during the hypotensive (sodium nitroprusside) and hypertensive (phenylephrine) phases of the modified Oxford were also assessed. There was no change in the overall R-R interval or hypotensive CVBRS during any of the hormone trials. Interestingly, the E group's CVBRS increased in response to the hypertensive stimulus, whereas the P group had no change. These data suggest that estradiol alone augments CVBRS to a hypertensive stimulus, but progesterone alone and combined E and P do not change CVBRS. Attenuated cardiovagal baroreflex sensitivity is associated with cardiovascular disease. Female sex hormones have a significant impact on the development of cardiovascular disease across the lifespan. Using an experimental model of hormone suppression and add-back, estradiol add-back alone increased cardiovagal baroreflex sensitivity to a hypertensive stimulus unlike the other hormone manipulation conditions. These data suggest that estradiol alone plays a significant role in cardiovagal baroreflex sensitivity and reductions may contribute to potential cardiovascular disease development.
随着年龄增长,女性的心血管迷走神经压力反射敏感性(CVBRS)下降幅度更大,这会导致心血管疾病风险升高。CVBRS减弱的一个潜在因素可能是雌激素减少。因此,我们检验了以下假设:单独使用雌二醇(E)以及联合使用雌二醇和孕酮(P)会在相同程度上增加CVBRS。为了研究E和P对健康绝经前女性CVBRS的急性影响,我们使用促性腺激素释放激素拮抗剂来抑制内源性性激素。我们在10 - 12天的激素处理过程中对29名年轻成年女性进行了测试。在激素抑制4天后,参与者每天接受0.1 - 0.2毫克经皮雌二醇(E)或200毫克口服微粉化孕酮(P)。在单独使用激素3 - 4天后,给予联合激素(200毫克孕酮和0.1 - 0.2毫克雌二醇)。在每次激素变化后约4天,按照改良牛津方案评估CVBRS。总体CVBRS被确定为R - R间期与收缩压之间反应的斜率。还评估了改良牛津方案中低血压(硝普钠)和高血压(去氧肾上腺素)阶段的CVBRS斜率。在任何激素试验期间,总体R - R间期或低血压CVBRS均无变化。有趣的是,E组的CVBRS对高血压刺激有反应性增加,而P组则无变化。这些数据表明,单独使用雌二醇可增强对高血压刺激的CVBRS,但单独使用孕酮以及联合使用E和P并不会改变CVBRS。心血管迷走神经压力反射敏感性减弱与心血管疾病相关。女性性激素在整个生命周期中对心血管疾病的发展有重大影响。使用激素抑制和补充的实验模型,与其他激素处理条件不同,单独补充雌二醇可增加对高血压刺激的心血管迷走神经压力反射敏感性。这些数据表明,单独使用雌二醇在心血管迷走神经压力反射敏感性中起重要作用,其降低可能有助于潜在心血管疾病的发展。