Venous Hemodynamic Function in Older Hypertensive Adults

虽然在老年人和高血压人群中对循环的动脉侧进行了广泛的研究，但对静脉系统的了解要少得多。静脉血流动力学功能随着年龄的增长而下降，并与高血压的病理生理学有关。动物模型提供的证据表明，静脉血流动力学功能改变的发展和建立阶段的高血压，但数据是缺乏在人类。考虑到高血压的患病率估计为5000万，并且老年美国人受到不成比例的影响，这是相关的。因此，这项建议将提供深入了解静脉顺应性的年龄和疾病相关的改变的机制。静脉壁的结构变化预计将主导静脉顺应性的年龄相关差异（类似于循环的动脉侧发生的情况），但静脉平滑肌张力和反应性的改变被假设为疾病相关差异的基础。为了实现这些目标，将采用横断面研究设计，利用四个不同的组：年轻血压正常，年轻高血压，老年血压正常，老年高血压成人（析因研究设计）。将使用最近验证的无创方法（Halliwill等人）。将绘制个体前臂和腿部压力-容积关系，并使用二次回归建模，以生成顺应性曲线。将在基础条件下、舌下含服硝酸甘油给药后和缺血性握力运动期间（限制性随机化）生成曲线，以分别检查平滑肌松弛和交感神经介导的收缩对静脉顺应性的影响。这些研究的结果将大大促进我们对老年血压正常和高血压成人静脉功能的理解，可能导致高血压治疗的创新治疗方法。本R 03提案的资金将允许P.I.提交后续R 01，重点关注以下衰老相关领域之一：（1）静脉血液动力学功能在高血压发展中的作用，（2）纵向耐力运动训练计划对静脉血液动力学功能的影响，（3）血管/静脉收缩剂内皮素-1对老年人静脉血液动力学功能的潜在病理影响。

While the arterial side of the circulation has been extensively studied in older and hypertensive humans, much less is known about the venous system. Venous hemodynamic function declines with age and has been implicated in the pathophysiology of hypertension. Animal models provide evidence that venous hemodynamic function is altered in the development and established phases of hypertension, yet data are lacking in humans. This is relevant considering the prevalence of hypertension is estimated to be 50 million, and older Americans are disproportionately affected. Thus, this proposal will provide insight into the mechanisms underlying age- and disease-related alterations in venous compliance. Structural changes in the walls of the veins are expected to dominate the age-related differences in venous compliance (similar to what occurs on the arterial side of the circulation), but alterations in venous smooth muscle tone and responsiveness are hypothesized to underlie the disease-related differences. In order to accomplish these aims, a cross sectional study design will be employed, utilizing four distinct groups: young normotensive, young hypertensive, older normotensive, and older hypertensive adults (factorial study design). A recently validated noninvasive approach (Halliwill et al) will be utilized. Individual forearm and leg pressure-volume relationships will be plotted and modeled using a quadratic regression to generate compliance curves. Curves will be generated under basal conditions, following sublingual nitroglycerin administration and during ischemic handgrip exercise (restricted randomization), to examine the effect of smooth muscle relaxation and sympathetically mediated contraction, respectively, on venous compliance. The findings from these studies will significantly advance our understanding of venous function in older normotensive and hypertensive adults, possibly leading to innovative therapeutic approaches for the treatment of hypertension. Funding of this R03 proposal will allow the P.I. to submit a subsequent R01 focused on one of the following aging-related areas: (1) the role of venous hemodynamic function in the development of hypertension, (2) the effects of a longitudinal endurance exercise training program on venous hemodynamic function, (3) and the potential pathologic effects of the vaso/venoconstrictor endothelin-1 on venous hemodynamic function in older adults.