Neural and Renal Contributions to Hypertension with Androgen Deprivation Therapy

项目摘要/摘要 候选人：马修·C·巴布科克博士，科罗拉多大学安舒茨分校助理教授 医学校园(CU-AMC)。Babcock博士的目标是研究神经和肾脏对高血压的贡献 雄激素剥夺疗法(ADT)。他开发的初步数据表明，1)身体较低的男性 与睾酮水平较高的男性相比，睾酮浓度降低了男性对压力感受器反射的敏感性 2)这些个体的压力反射敏感性与循环中的血药浓度相关。 促炎细胞因子白介素6。在这份提案中，他将通过综合翻译这些数据 评估接受ADT的男性对血压的神经控制，并将他的观察扩展到包括 肾对血压的控制。中心假设是ADT增加炎症，从而减少 压力感受性反射敏感性，增加交感神经反应性，增加肾血管阻力。职业生涯 发展计划：巴布科克博士建议通过以下方式加强自己的职业发展：1)掌握新技能 在评估肾血浆流量、评估肾功能生物标志物和评估PRO。 炎症细胞因子；2)肾脏疾病和生理学高级培训；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指导下对他们进行ADT研究 伊丽莎白·凯斯勒博士，一位专门研究前列腺癌的内科肿瘤学家；以及4)完善他的专业 通过正式的课程作业、出席和在每周科学进步和重大会议上的演讲来掌握技能 在巡回会议和国家科学会议上。环境：巴布科克博士将在一项杰出的研究中接受培训 由多学科导师团队提供支持的环境。主要导师莫罗博士是一名NIA- 在CU-AMC获得资助的教授，有成功指导的记录。她是性激素作用方面的专家 以及炎症对心血管功能的影响。她在利用性腺抑制方面有丰富的经验。 本研究提出了研究设计方案。共同导师威廉·康威尔博士也是CU-AMC的一名专家 对血液循环的自主控制。共同导师杰西卡·肯德里克博士和顾问皮特·比约恩斯塔德博士也是 CU-AMC和研究肾功能的专家。凯斯勒博士是前列腺癌和ADT方面的专家。 乔伊纳和法夸尔是自主神经功能和运动升压反射方面的专家。 研究：ADT是前列腺癌管理的支柱和令人印象深刻的存活率 被诊断为前列腺癌的男性在很大程度上归功于ADT的有效性。然而，ADT 增加患高血压的可能性，从而增加接受治疗的前列腺癌幸存者的风险 与不接受ADT治疗的男性相比，患有ADT的男性更有可能死于心血管疾病 ADT.迫切需要阐明心血管疾病风险增加的潜在机制。 在这些患者中改善前列腺癌幸存者的生活。

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.