SENESCENCE ALTERS SYMPATHETIC REGULATION TO HEAT STRESS

高温和心血管疾病的过度死亡发生在热浪期间的老年人中，然而，对相关机制知之甚少。 由于交感神经系统在心血管调节热应激中起着关键作用，我们假设衰老大鼠心血管对加热的改变可能是由于交感神经调节的年龄相关变化。 与这一假设相一致，我们的初步数据表明，肾交感神经放电（SND）的反应，急性热应激衰减衰老。 （24月龄）与成熟（10月龄）F344大鼠相比;然而，责任机制尚未得到很好的理解。拟议的研究将确定老年大鼠对热应激的SND反应减弱的机制。 具体目标1：检验衰老大鼠静息时传出SND水平不代表生理最大值或最小值的假设。 具体目标二：确定衰老是否改变了SND调节机制，从而使衰老F344大鼠与成熟F344大鼠在热应激期间使用不同的神经策略。 我们将检验以下假设：a）与成熟大鼠相比，高血压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）衰老与Tc增加期间交感神经回路的反应特征的变化相关，如SND爆发模式缺乏改变所证明的，以及c）在衰老但不成熟的F344大鼠中，内脏器官和尾部血流在急性加热期间保持不变。 具体目标3：检验衰老大鼠急性发热激活选定的体温调节效应子的假设。具体目标4：确定是否前脑神经回路，特别是下丘脑室旁核，是关键参与抑制SND反应的热应激在衰老大鼠。 将使用电生理学、CNS损伤和灌注以及频域分析技术来完成这些研究。拟议的研究将首次提出这样一个假设，即交感神经回路对热应激作出反应的工作策略会因衰老而改变。

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.