Venous Hemodynamic Function in Older Hypertensive Adults

虽然在老年人和高血压患者中已经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，在高血压的发展和建立阶段，静脉血流动力学功能会发生变化，但在人类身上缺乏数据。考虑到高血压的患病率估计为5000万，而且美国老年人受到的影响不成比例，这一点是相关的。因此，这项建议将提供对年龄和疾病相关的静脉顺应性改变的潜在机制的洞察。静脉壁的结构变化预计将主导与年龄相关的静脉顺应性差异(类似于循环动脉侧的情况)，但假设静脉平滑肌张力和反应性的变化是与疾病相关的差异的基础。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：青年正常血压组、青年高血压组、老年正常血压组和老年高血压组(析因研究设计)。将使用最近经过验证的非侵入性方法(Halliwill等人)。单个前臂和腿部压力-体积关系将被绘制出来，并使用二次回归进行建模，以生成顺应性曲线。在基础条件下，舌下注射硝酸甘油和缺血握力运动(受限随机)下，将产生曲线，以分别检测平滑肌松弛和交感神经调节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血压正常和高血压的老年成年人静脉功能的了解，可能导致治疗高血压的创新治疗方法。这份R03提案的资金将使P.I.能够提交后续的R01，重点关注以下与衰老相关的领域之一：(1)静脉血流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流动力学功能的影响，(3)血管/静脉收缩素-1对老年人静脉血流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.