Neural and Renal Contributions to Hypertension with Androgen Deprivation Therapy

雄激素剥夺疗法对高血压的神经和肾脏影响

• 批准号: 10662133
• 负责人: Matthew C Babcock
• 金额: $ 16.62万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-08-01 至 2028-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10662133
• 关键词: Accounting; Acute Renal Failure with Renal Papillary Necrosis; Adverse effects; Affect; Agonist; American; Androgen Receptor; Androgen Suppression; Androgens; Baroreflex; Biological Markers; Blood Pressure; Brain Stem; Cancer Survivor; Cancer Survivorship; Cardiovascular Diseases; Cardiovascular Physiology; Cardiovascular system; Cause of Death; Cessation of life; Circulation; Clinical; Colorado; Data; Development Plans; Diagnosis; Distal; Doctor of Philosophy; Effectiveness; Environment; Exercise; Functional disorder; Funding; Future; Glomerular Filtration Rate; Goals; Gonadal Steroid Hormones; Gonadotropin Hormone Releasing Hormone; Growth; Heart Rate; Hormones; Human; Hypertension; IL18 gene; Impaired Renal Function; Impairment; Individual; Inflammation; Inflammatory; Interleukin-6; Isometric Exercise; Kidney; Kidney Diseases; LCN2 gene; Liver; Longitudinal Studies; Malignant Neoplasms; Malignant neoplasm of prostate; Measures; Medical; Medical Oncologist; Mentors; Mentorship; Metastatic Prostate Cancer; Microinjections; Nerve; Neuronal Dysfunction; Neurophysiology - biologic function; Observational Study; Outcome; Patients; Physiology; Placebo Control; Placebos; Population; Pre-Clinical Model; Prostate Cancer therapy; Proteomics; Randomized Controlled Clinical Trials; Rattus; Receptor Inhibition; Recording of previous events; Reflex action; Renal Blood Flow; Renal Plasma Flow; Renal function; Research; Research Design; Research Personnel; Resistance; Risk; Rodent; Role; Scientific Advances and Accomplishments; Secure; Survival Rate; System; Technical Expertise; Testing; Testosterone; Time; Training; Translating; Tubular formation; Universities; Vascular resistance; Work; androgen deprivation therapy; arm; aspirate; blood pressure control; blood pressure elevation; blood pressure regulation; blood pressure variability; cardiovascular disorder risk; cardiovascular health; cardiovascular risk factor; career development; cytokine; experience; fatty acid-binding proteins; improved; inhibitor; insight; kidney dysfunction; kidney vascular structure; meetings; men; middle age; modifiable risk; mortality; multidisciplinary; neural; neural circuit; neuroregulation; older men; professor; prostate cancer survivors; rat KIM-1 protein; recruit; response; side effect; skills; vasoconstriction

PROJECT SUMMARY / ABSTRACT CANDIDATE: Matthew C. Babcock, Ph.D. is an Assistant Professor at the University of Colorado Anschutz Medical Campus (CU-AMC). Dr. Babcock aims to study the neural and renal contributions to hypertension with androgen deprivation therapy (ADT). He has developed preliminary data indicating that 1) men with lower testosterone concentrations have reduced baroreflex sensitivity compared to men with higher testosterone concentrations; and 2) baroreflex sensitivity in these individuals is correlated with circulating concentrations of the proinflammatory cytokine interleukin-6. In this proposal, he will translate these data by comprehensively assessing neural control of blood pressure in men who undergo ADT, and extend his observations to include renal control of blood pressure. The central hypothesis is that ADT increases inflammation and thereby reduces baroreflex sensitivity, increases sympathetic reactivity, and increases renovascular resistance. CAREER DEVELOPMENT PLAN: Dr. Babcock proposes to enhance his career development by: 1) acquiring new skills in the assessment of renal plasma flow, assessment of renal function biomarkers, and assessment of pro- inflammatory cytokines; 2) Advanced training renal diseases and physiology; 3) Working with a clinical population by recruiting men diagnosed with prostate cancer and studying them while they undergo ADT under the guidance of Dr. Elizabeth Kessler, a medical oncologist who specializes in prostate cancer; and 4) Refining his professional skills through formal course work, attendance and presentations at weekly Scientific Advancement and Grand Rounds, and at national scientific meetings. ENVIRONMENT: Dr. Babcock will train in an outstanding research environment supported by a multi-disciplinary team of mentors. The primary mentor, Dr. Moreau, is an NIA- funded professor at CU-AMC with a record of successful mentorship. She is an expert in the role of sex hormones and inflammation on cardiovascular function. She has extensive experience in utilizing the gonadal suppression study design proposed in the current study. Co-Mentor Dr. William Cornwell, III is also at CU-AMC and an expert in autonomic control of the circulation. Co-Mentor Dr. Jessica Kendrick and advisor Dr. Petter Bjornstad are also at CU-AMC and experts in studying renal function. Advisor Dr. Kessler is an expert in prostate cancer and ADT. Advisor Drs. Joyner and Farquhar are experts in autonomic function and the exercise pressor reflex. RESEARCH: ADT is a mainstay in the management of prostate cancer and the impressive survival rates among with men diagnosed with prostate cancer is largely attributed to the effectiveness of ADT. However, ADT increases the likelihood of developing hypertension and, accordingly, prostate cancer survivors who were treated with ADT are more likely to die early from cardiovascular diseases compared to men treated without the use of ADT. There is a critical need to elucidate the mechanisms underlying the increased cardiovascular disease risk in these patients to improve the lives of prostate cancer survivors.

项目总结/摘要 候选人：马修C。Babcock博士是科罗拉多安舒茨大学的助理教授 医学院（CU-AMC）Babcock博士旨在研究神经和肾脏对高血压的贡献， 雄激素剥夺疗法（ADT）。他已经开发了初步数据表明：1）男性与低 与睾酮较高的男性相比，睾酮浓度降低了压力反射敏感性 浓度;和2）这些个体的压力反射敏感性与循环浓度相关， 促炎细胞因子白细胞介素-6。在这份提案中，他将全面翻译这些数据， 评估接受ADT的男性血压的神经控制，并将他的观察扩展到包括 肾控制血压。中心假设是ADT增加炎症，从而减少 压力反射敏感性，增加交感神经反应性，并增加肾血管阻力。职业生涯 发展方向：Babcock博士建议通过以下方式促进其职业发展：1）获得新技能 在肾血浆流量的评估、肾功能生物标志物的评估和促肾功能的评估中， 炎性细胞因子; 2）肾脏疾病和生理学高级培训; 3）临床人群工作 通过招募被诊断患有前列腺癌的男性，并在他们接受ADT的指导下对其进行研究， 伊丽莎白·凯斯勒博士，一位专门研究前列腺癌的医学肿瘤学家; 4）完善他的专业知识， 通过正式的课程工作，出席和介绍每周科学进步和盛大的技能 以及在国家科学会议上。环境：巴布科克博士将在一个杰出的研究培训 由多学科导师团队支持的环境。主要的导师，莫罗博士，是一个NIA- 在CU-AMC的资助教授与成功的指导记录。她是性激素作用方面的专家 和炎症对心血管功能的影响。她在利用性腺抑制方面经验丰富 本研究中提出的研究设计。共同导师威廉康威尔博士，三也是在CU-AMC和专家 自主控制血液循环共同导师Jessica Kendrick博士和顾问Petter Bjornstad博士也是 和研究肾功能的专家。Kessler博士是前列腺癌和ADT的专家。 顾问乔伊纳博士和法夸尔博士是自主神经功能和运动加压反射方面的专家。 研究：ADT是前列腺癌管理的支柱， 男性前列腺癌的治疗主要归功于ADT的有效性。然而，ADT 增加患高血压的可能性，因此，接受治疗的前列腺癌幸存者 与未使用ADT治疗的男性相比，使用ADT治疗的男性更有可能死于心血管疾病。 ADT。目前迫切需要阐明心血管疾病风险增加的潜在机制 来改善前列腺癌幸存者的生活。