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.

项目摘要 /摘要 候选人：Matthew C. Babcock博士是科罗拉多大学安苏兹大学的助理教授 医疗校园（CU-AMC）。 Babcock博士旨在研究对高血压的神经和肾脏贡献 雄激素剥夺疗法（ADT）。他已经制定了初步数据，表明1）较低的男性 与睾丸激素较高的男性相比 浓度； 2）这些个体中的压力反射灵敏度与循环浓度相关 促炎细胞因子白细胞素6。在此提案中，他将通过全面翻译这些数据 评估接受ADT的男性血压的神经控制，并扩展其观察结果 血压的肾脏控制。中心假设是ADT增加了炎症，从而减少了 压力反射灵敏度，提高交感神经反应性并增加肾血管耐药性。职业 发展计划：Babcock博士建议通过以下方式提高自己的职业发展 在评估肾脏等离子体流动，评估肾功能生物标志物以及促进评估 炎症细胞因子； 2）高级培训肾脏疾病和生理学； 3）与临床人群合作 通过招募被诊断为前列腺癌的男性并在接受ADT的指导下进行ADT研究 专门研究前列腺癌的医学肿瘤学家伊丽莎白·凯斯勒（Elizabeth Kessler）博士； 4）完善他的专业人士 通过正式的课程工作，出勤和演讲的技能，每周科学进步和盛大 巡回赛，以及在国家科学会议上。环境：Babcock博士将培训一项杰出的研究 由多学科导师团队支持的环境。主要导师Moreau博士是Nia- Cu-AMC教授的资助，并记录了成功的指导。她是性激素角色的专家 和心血管功能的炎症。她在利用性腺抑制方面拥有丰富的经验 当前研究中提出的研究设计。联盟人威廉·康威尔（William Cornwell）博士，III也在Cu-AMC和专家 在循环的自主控制中。杰西卡·肯德里克（Jessica Kendrick）博士和顾问Petter Bjornstad博士也是 在Cu-AMC和研究肾功能的专家。顾问凯斯勒博士是前列腺癌和ADT的专家。 顾问Drs。乔伊纳（Joyner）和法夸（Farquhar）是自主功能的专家和运动式训练反射。 研究：ADT是前列腺癌管理和令人印象深刻的生存率的支柱 由于被诊断出患有前列腺癌的男性在很大程度上归因于ADT的有效性。但是，adt 增加了患高血压的可能性，因此，接受治疗的前列腺癌幸存者 与未经使用的男性相比 adt。迫切需要阐明心血管疾病风险增加的机制 在这些患者中，改善了前列腺癌幸存者的生活。