Mechanisms of exertional hypertension and vascular dysfunction

描述（由申请人提供）： 长期以来，由于有氧能力和血管内皮一氧化氮（NO）生物利用度的改善，体力活动与心脏病的发病率和死亡率降低有关。尽管抗阻运动对NO生物利用度的影响知之甚少，但最近的流行病学证据表明，举重训练与有氧运动类似，与心脏事件的减少相关。然而，抗阻运动的好处是复杂的事实，急性高血压在举重可能是有害的内皮功能。因此，本提案的总体目标是确定慢性阻力训练对内皮功能和NO生物利用度是否有益或有害。该假说认为，急性高血压在抗阻运动中通过增加活性氧（ROS）的产生和减少可用的一氧化氮（NO）而损害非条件性久坐患者的动脉和小动脉内皮功能。本提案将检验以下假设：1）运动I高血压在久坐受试者中产生的ROS和炎性介质的增加大于有氧或阻力训练的运动员; 2）举重后久坐受试者中内皮功能降低的机制涉及ROS产生的增加。这些研究的结果将影响向有心血管疾病风险的患者提供的特定运动建议的模式和强度。该研究计划与职业发展计划相结合，将申请人在基础血管生物学方面的优势与评估人类血管健康相结合。候选人Shane菲利普斯博士正在从研究培训职位过渡到威斯康星州医学院的教员职位。他的职业目标是成为人类血管生物学领域的独立翻译研究者，这项提议将为这一转变提供支持性的研究环境和机构支持。职业发展计划利用最先进的血管技术和教学培训，面向临床相关问题的调查，同时建立在他以前的物理治疗临床培训和血管生物学博士培训的基础上。大卫Gutterman博士，一个既定的翻译研究员，将在候选人的独立研究生涯的初始阶段提供指导。(End摘要）

DESCRIPTION (provided by applicant): Physical activity has long been associated with lower morbidity and mortality from heart disease owing to improvements in aerobic capacity and vascular endothelial nitric oxide (NO) bioavailability. While much less is known about the effects of resistance exercise on NO bioavailability recent epidemiological evidence indicate that weight training is correlated with a reduction in cardiac events similar to aerobic exercise. However, the benefits of resistance exercise are complicated by the fact that acute hypertension during weight lifting may be detrimental to endothelial function. Therefore, the overall goal of this proposal is to determine whether chronic resistance training is beneficial or detrimental to endothelial function and NO bioavailibility. The hypothesis is that acute hypertension during resistance exercise impairs arterial and arteriolar endothelial function in non-conditioned sedentary patients by increasing reactive oxygen species (ROS) generation and reducing available nitric oxide (NO). This proposal will test the following hypotheses 1) exertions I hypertension produces a greater increase in ROS and inflammatory mediators in sedentary subjects than in aerobic or resistance trained athletes; and 2) the mechanism of reduced endothelial function in sedentary subjects following weightlifting involves an increase in ROS generation. The results of these studies will impact the mode and intensity of specific exercise recommendations given to patients at risk for cardiovascular disease. This research proposal coupled with the career development program integrates the strengths of the applicant in fundamental vascular biology with assessment human vascular health. The candidate Dr. Shane Phillips is transitioning from a research training position to that of a faculty member at the Medical College of Wisconsin. His career goal is to become an independent translational investigator in the field of human vascular biology and this proposal will provide a supportive research environment as well as institutional support for this transition. The career development plan utilizes state of the art vascular techniques and didactic training geared toward the investigation of clinically relevant questions while building on his previous clinical training in physical therapy and doctoral training in vascular biology. Dr. David Gutterman, an established translational researcher, will provide mentorship during the initial stages of the candidates' independent research career. (End of Abstract)