Vascular regulation in postmenopausal females

项目概要/摘要 这项拟议研究的目标是阐明导致高风险的机制， 与典型年龄组相比，绝经早期心血管疾病（CVD）和高血压（HTN） 更年期女性CVD和HTN的风险在绝经后急剧增加，但完成绝经的女性 绝经早（<46岁）更有可能经历HTN和CVD相关的发病率和死亡率 在典型年龄（~ 51岁）完成绝经的人此外，交感神经增加， 女性绝经后，更高的交感神经驱动与心血管死亡率和HTN相关。 绝经后女性的血压自主控制功能失调，但这是一个很大的问题。 尚不清楚早期绝经和典型年龄绝经女性的血压失调是否相似。 此外，改变的血管传导，由此交感神经活动的增加引起血管收缩， 可能在HTN的发展中发挥作用。这项建议将调查交感神经调节血流 和绝经早期和典型年龄女性的血压。此外，被种族化的人 因为非白色人比白色人有更高的心血管风险，这项研究将探讨 歧视和应对是不同年龄绝经后女性CVD和HTN的潜在介质 背景评价血管调节、前臂血管传导性（FVC）和肌肉交感神经功能 神经活动（MSNA）将通过静脉闭塞体积描记术和显微神经描记术来测量， 分别在绝经后女性，年龄50-70岁，提前或在典型的 年龄将在静息（SA 1）和两分钟冷加压试验（CPT）期间测量电导和MSNA 手（SA 2）重要的是，血压对CPT的反应可以预测未来的HTN，以及更大的交感神经反应。 对应激源的反应性可能表明未来CVD的风险更高。此外，生理反应和 将探讨歧视和应对得分之间的相关性（SA 3）。假设是早期- 绝经期女性的静息FVC较低，静息MSNA较高，FVC和MSNA的变化较大， MSNA与CPT，比典型年龄绝经女性;和较高的感知歧视和较低的 应对能力将与较高的交感神经流出相关。李博士将接受 显微神经描记术和静脉闭塞体积描记术，并将从事职业发展活动， 包括助学金和奖学金的发展。此外，她还将接受社区参与培训， 奖学金期间的策略。她将在一个研究丰富的 在明尼苏达大学医学院的环境。该提案与NHLBI的 使命，确定有助于高血压和心血管疾病预防和治疗的机制 降低绝经早期女性心血管疾病风险的策略，同时努力实现健康公平。的 拟议的研究将提供基础知识沿着与特殊的奖学金培训的申请人。

Project Summary/Abstract The goal of the proposed study is to elucidate mechanisms contributing to the heightened risk of cardiovascular disease (CVD) and hypertension (HTN) in early-menopausal compared to typical-age- menopausal females. The risks of CVD and HTN increase steeply after menopause, but females who complete menopause early (< age 46 yrs.) are more likely to experience HTN and CVD-related morbidity and mortality than those who complete menopause at a typical age (~ 51 yrs.) Furthermore, sympathetic increases in females after menopause, and higher sympathetic drive is associated with cardiovascular mortality and HTN. Postmenopausal females have shown dysregulation in autonomic control of blood pressure (BP), but it is unknown whether BP dysregulation occurs similarly in early-menopausal and typical-age-menopausal females. Moreover, altered vascular transduction, whereby an increase in sympathetic activity causes vasoconstriction, may play a role in the development of HTN. This proposal will investigate sympathetic regulation of blood flow and blood pressure in early- and typical-age-menopausal females. Additionally, individuals who are racialized as non-white have higher cardiovascular risks than white people, and this study will explore perceived discrimination and coping as potential mediators of CVD and HTN in postmenopausal females of diverse backgrounds. To evaluate vascular regulation, forearm vascular conductance (FVC) and muscle sympathetic nerve activity (MSNA) will be measured via venous occlusion plethysmography and microneurography, respectively, in postmenopausal females, ages 50-70 yrs., who completed menopause early or at a typical age. Conductance and MSNA will be measured at rest (SA1) and during a two-minute cold pressor test (CPT) of the hand (SA2). Importantly, BP responses to a CPT can predict future HTN, and greater sympathetic reactivity to a stressor may indicate a higher risk for future CVD. Further, physiological responses and correlations between discrimination and coping scores will be explored (SA3). The hypotheses are that early- menopausal females will have lower resting FVC and higher resting MSNA, and larger changes in FVC and MSNA with CPT, than typical-age-menopausal females; and that higher perceived discrimination and lower coping ability will be associated with higher sympathetic outflow. Dr. Lee will be trained in techniques of microneurography and venous occlusion plethysmography and will engage in career development activities, including grant and scholarship development. In addition, she will be trained in community-engagement strategies during the fellowship duration. She will receive training from an exemplary team in a research-rich environment within the Medical School at the University of Minnesota. This proposal aligns with the NHLBI’s mission, identifying mechanisms contributing to HTN and CVD for development of prevention and treatment strategies to reduce CVD risk in early-menopausal females, while also striving toward health equity. The proposed study will provide foundational knowledge along with exceptional fellowship training for the applicant.