Vascular regulation in postmenopausal females

绝经后女性的血管调节

• 批准号: 10462980
• 负责人: Emma J Lee
• 金额: $ 7.43万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-04-16 至 2024-10-15
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10462980
• 关键词: Age; Aging; Award; Blood Pressure; Blood Vessels; Blood flow; Cardiac; Cardiovascular Diseases; Cardiovascular Physiology; Cardiovascular system; Cause of Death; Communities; Data; Development; Development Plans; Discrimination; Environment; Estrogens; Ethnic Origin; Fellowship; Female; Forearm; Foundations; Functional disorder; Future; Goals; Gonadal Steroid Hormones; Grant; Hand; Health; Hypertension; Impairment; Individual; Knowledge; Link; Measures; Mediator of activation protein; Menopause; Mentors; Minnesota; Mission; Morbidity - disease rate; Muscle; National Heart, Lung, and Blood Institute; Nerve; Outcome; Participant; Patients; Persons; Physiological; Physiology; Play; Plethysmography; Population Heterogeneity; Postmenopause; Premature Menopause; Premenopause; Prevalence; Prevention approach; Prevention strategy; Regulation; Research; Rest; Risk; Risk Factors; Role; Scholarship; Stress; Sympathetic Nervous System; Techniques; Testing; Therapeutic; Training; United States; United States National Institutes of Health; Universities; Vascular resistance; Venous; Work; blood pressure control; blood pressure elevation; blood pressure regulation; burden of illness; cardiovascular disorder risk; cardiovascular health; cardiovascular risk factor; career; career development; coping; economic impact; ethnic diversity; experience; health economics; health equity; high risk; improved; indexing; insight; medical schools; mortality; perceived discrimination; prophylactic; racial population; resilience; response; stressor; targeted treatment; treatment strategy; vasoconstriction

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.

项目摘要/摘要 这项拟议的研究的目标是阐明导致高血压风险增加的机制。 与典型年龄相比，绝经早期的心血管疾病(CVD)和高血压(HTN) 更年期的女性。绝经后患心血管疾病和HTN的风险急剧增加，但完成 绝经早(&lt；岁46岁)更有可能经历HTN和CVD相关的发病率和死亡率 比那些在典型年龄(约51岁)完成更年期的人更多。此外，同情心增加了 女性绝经后，交感神经驱动力较高与心血管死亡率和HTN相关。 绝经后的女性在自主控制血压方面表现出失调，但事实并非如此 尚不清楚在绝经早期和典型绝经年龄的女性中是否也会发生血压失调。 此外，交感神经活动的增加会引起血管收缩，从而改变血管传导， 可能在HTN的发展中发挥作用。这项提案将研究交感神经对血流的调节。 以及绝经早期和典型年龄女性的血压。此外，被种族歧视的个人 因为非白人比白人有更高的心血管风险，这项研究将探索 歧视和应对是不同性别绝经后女性心脑血管疾病和神经官能症的潜在中介因素 背景。评估血管调节、前臂血管传导性(FVC)和肌交感 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进行测量， 分别在50-70岁的绝经后女性中，提前或典型地完成绝经的女性 年龄。电导和MSNA将在静止状态(SA1)和两分钟冷加压试验(CPT)中测量 手部(SA2)。重要的是，BP对CPT的反应可以预测未来的HTN，并且更有同情心 对应激源的反应可能预示着未来心血管疾病的风险更高。此外，生理反应和 本课程将探讨歧视与应对分数之间的关系(SA3)。假设是早期的- 更年期女性的静息FVC和MSNA较低，而FVC和MSNA的变化较大。 患有CPT的MSNA高于典型年龄更年期女性；更高的知觉歧视和更低的歧视 应对能力将与更高的交感流出相关。李博士将接受技术培训 显微神经学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方面的培训 团契期间的策略。她将接受一个研究丰富的模范团队的培训 明尼苏达大学医学院内的环境。这项建议与NHLBI的 任务，确定促进HTN和CVD的机制，以制定预防和治疗 减少绝经早期女性心血管疾病风险的战略，同时也努力实现健康公平。这个 拟议的研究将为申请者提供基础知识和特殊的奖学金培训。