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细胞一氧化氮(NO)生物利用度的提高，体力活动与心脏病的发病率和死亡率降低有关。虽然阻力运动对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，举重训练与心脏事件的减少有关，类似于有氧运动。然而，阻力运动的好处是复杂的，因为举重过程中的急性高血压可能会损害内皮功能。因此，这项建议的总体目标是确定慢性耐力训练对内皮功能是有益还是有害，而不是生物利用度。假设阻力运动中的急性高血压通过增加活性氧(ROS)的产生和减少有效的一氧化氮(NO)来损害非条件久坐患者的动脉和小动脉内皮功能。这项建议将检验以下假设：1)与有氧或阻力训练的运动员相比，高血压在久坐的受试者中产生更大的ROS和炎症介质的增加；以及2)举重后久坐受试者内皮功能下降的机制涉及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特定运动建议的模式和强度。这项研究建议与职业发展计划相结合，将申请者在基础血管生物学方面的优势与评估人类血管健康结合在一起。候选人谢恩·菲利普斯博士正在从威斯康星医学院的研究培训职位过渡到教员职位。他的职业目标是成为人类血管生物学领域的一名独立翻译研究员，这一提议将为这一过渡提供一个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，旨在调查临床相关问题，同时建立在他之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·古特曼博士是一位知名的翻译研究员，他将在候选人独立研究生涯的初始阶段提供指导。(摘要结束)

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)