AGE AND CONTROL OF HUMAN SKIN BLOOD FLOW

描述(改编自申请人的摘要)：皮肤 血液循环在人体体温调节中起着不可或缺的作用。确实有 皮肤中真皮基质中与年龄相关的固有变化 血管以及血液流动的自主控制，其中任何一个或全部可以 改变皮肤血管对局部和全身热的反应 压力。在授予AG07004-01至-05期间进行的研究 说明在热应激期间，皮肤血流量增加 (SkBF)和体心每摄氏度增加的皮肤血管电导 健康活跃的男性和女性的体温显著降低 55岁，与20-30岁的受试者相比。这一减量 似乎是由于外周而不是中枢(例如，下丘脑) 与年龄相关的变化。然而，仍有许多关于老龄化和 控制皮肤血液流动。人体对抬高身体的SkBF反应 温度的独特之处在于有一种发育良好的活性 交感血管扩张系统和肾上腺素能血管收缩药 系统。在任何一组给定的环境影响下，平衡 这两个相互竞争的系统之间的关系决定了净SkBF，但它是 不知道哪个系统会因老化过程而改变。当地人 消除血管收缩作用的对甲苯磺酸布雷酯的离子导入 影响，从而允许研究活性血管扩张剂 系统在没有收缩效应的情况下-提供了一种工具 以检查内在影响的潜在机制 年龄对SkBF控制的影响。此外，针对以下目标的干预措施 增加老年受试者的热诱导血管扩张并没有 被检查过了。因此，拟议延续的范围 格兰特AG-07004是系统地研究年龄对 人类皮肤血液流动的控制，以及年龄背后的机制- 相关变化。具体研究假设如下：1)体内 最大血容量随年龄增长而降低；2)传出通路 与随着年龄增长而减弱的血管扩张反应有关的是 活跃的血管扩张系统；3)与年龄相关的SkBF下降可 因运动训练而变弱；3a)负责的机制是 在给定的核心温度下增强血管扩张系统的活性；4) 绝经后妇女，雌激素(E2)替代疗法增加SkBF 在给定的核心温度下；a)该响应次于E2- 诱发等渗性高容量血症。

DESCRIPTION (Adapted from the applicant's abstract): The cutaneous circulation plays an integral role in human thermoregulation. There are intrinsic age-related changes in the dermal matrix, in the cutaneous vessels, and in autonomic control of blood flow, any or all of which may alter the cutaneous vascular response to local and whole-body thermal stresses. Studies performed under Grant AG07004-01 through -05 demonstrated that during heat stress, the increase in skin blood flow (SkBF) and skin vascular conductance per degree C increment in body core temperature is markedly attenuated in healthy active men and women over the age of 55, when compared to 20-30 year- old subjects. This decrement appears to be due to peripheral rather than central (e.g., hypothalamic) age-related changes. However, many questions remain about aging and control of skin blood flow. The human SkBF response to elevated body temperature is unique in that there is a well developed active sympathetic vasodilator system as well as an adrenergic vasoconstrictor system. Under any given set of environmental influences, the balance between these two competing systems determines the net SkBF, yet it is not known which system is altered by the aging process. The local iontophoresis of bretylium tosylate - which eliminates vasoconstrictor influences, and thus allows for the study of the active vasodilator system in the absence of constrictor effects - provides a tool with which to examine the mechanisms underlying the effects of intrinsic aging on control of SkBF. In addition, interventions aimed at increasing thermally-induced vasodilation in older subjects have not been examined. Therefore, the scope of the proposed continuation of Grant AG- 07004 is to systematically study the effects of age on the control of human skin blood flow, and the mechanisms underlying the age- related changes. Specific research hypotheses are as follows: 1) In vivo maximal SkBF decreases with advancing age; 2) The efferent pathway involved in the attenuated vasodilatory response with aging is the active vasodilator system; 3) The age- related decline in SkBF can be attenuated by exercise training; 3a) The mechanism responsible is enhanced vasodilator system activity at a given core temperature; 4) In post-menopausal women, estrogen (E2) replacement therapy increases SkBF at a given core temperature; a) This response is secondary to an E2- induced isotonic hypervolemia.