SENESCENCE ALTERS SYMPATHETIC REGULATION TO HEAT STRESS

高温和心血管疾病导致的高死亡率发生在热浪期间的老年人中，然而，相关机制尚不清楚。由于交感神经系统在心血管对热应激的调节中起着关键作用，我们假设衰老大鼠心血管对加热的改变可能是交感神经调节的年龄相关变化引起的。与这一假设一致，我们的初步数据表明，肾脏交感神经放电（SND）对急性热应激的反应在衰老中减弱。（24月龄）与成熟（10月龄）F344大鼠比较；然而，有关的机制还没有得到很好的理解。提出的研究将确定老龄大鼠对热应激的SND反应减弱的机制。具体目的1：验证衰老大鼠休息时输出SND水平不代表生理最大值或最小值的假设。特定目的2：确定衰老是否会改变SND调节机制，从而使衰老大鼠与成熟F344大鼠在热应激过程中使用不同的神经策略。我们将验证以下假设：a)与成熟大鼠相比，高温诱导的交感神经兴奋和交感神经抑制反应在衰老大鼠中减弱；b) SND破裂模式缺乏改变证明，衰老与Tc增加期间交感神经回路的反应特征变化有关；c)衰老而非成熟F344大鼠在急性加热期间内脏器官和尾部血流保持不变。具体目的3：验证衰老大鼠急性加热激活选定的热调节效应的假设。特定目的4：确定是否前脑神经回路，特别是下丘脑室旁核，在抑制衰老大鼠对热应激的SND反应中起关键作用。电生理学，中枢神经系统损伤和灌注，以及频域分析技术将被用于完成这些研究。提出的研究将首次提出交感神经回路对热应激反应的工作策略随着年龄的增长而改变的假设。

Excess mortality from hyperthermia and cardiovascular disease occurs in aged humans during heat waves, however, responsible mechanisms are poorly understood. Because the sympathetic nervous system plays a critical role in cardiovascular regulation to heat stress, we hypothesize that cardiovascular alterations to heating in senescent rats may result from age-related changes in sympathetic nerve regulation. Consistent with this hypothesis, our preliminary data demonstrate that renal sympathetic nerve discharge (SND) responses to acute heat stress are attenuated in senescent. (24-month-old) compared with mature (10-month-old) F344 rats; however the responsible mechanisms are not well understood. The proposed studies will determine mechanisms responsible for the diminished SND responses to heat stress in aged rats. Specific Aim 1: Test the hypothesis that levels of efferent SND at rest in senesent rats do not represent the physiological maximum or minimum. Specific Aim 2: To determine if aging alters SND regulatory mechanisms such that different neural strategies are used during heat stress in senescent compared to mature F344 rats. We will test the hypotheses that: a) hyperthermia-induced sympathoexcitatory and sympathoinhibitory responses are attenuated in senescent compared to mature rats, b) aging is associated with changes in the response characteristics of sympathetic neural circuits during increased Tc as demonstrated by the lack of alterations in the SND bursting pattern, and c) visceral organ and tail blood flows remain unchanged during acute heating in senescent but not mature F344 rats. Specific Aim 3: Test the hypothesis that acute heating in senescent rats activates selected thermoregulatory effectors. Specific Aim 4: To determine if forebrain neural circuits, specifically the paraventricular nucleus of the hypothalamus, are critically involved in suppressing SND responses to heat stress in senescent rats. Electrophysiological, CNS lesioning and perfusion, and frequency-domain analytical techniques will be used to complete these studies. The proposed studies will, for the first time, advance the hypothesis that the working strategies employed by sympathetic neural circuits to respond to heat stress are modified by aging.