SENESCENCE ALTERS SYMPATHETIC REGULATION TO HEAT STRESS

衰老改变了对热应激的交感调节

基本信息

批准号：
6740149
负责人：
Michael J Kenney
金额：
$ 21.83万
依托单位：
KANSAS STATE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2001
资助国家：
美国
起止时间：
2001-07-01 至 2006-05-31
项目状态：
已结题

项目摘要

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.

热浪期间，高温和心血管疾病的死亡率过多发生，但是，负责任的机制知之甚少。由于交感神经系统在心血管调节中对热应激起着至关重要的作用，因此我们假设衰老大鼠加热的心血管改变可能是由于年龄相关的交感神经调节变化而引起的。与这一假设一致，我们的初步数据表明，肾交感神经排出（SND）对急性热应激的反应在衰老中减弱。（24个月大）与成熟（10个月大的）F344大鼠相比；但是，负责任的机制尚不清楚。拟议的研究将确定负责老年大鼠热应激反应减少的机制。特定目的1：检验以下假设：senesent大鼠中静止的SND水平并不代表生理最大或最小值。具体目的2：确定衰老是否改变了SND调节机制，与成熟的F344大鼠相比，衰老期间使用了不同的神经策略。 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衰老但不成熟的F344大鼠。具体目标3：检验衰老大鼠急性加热的假设会激活选定的热调节效应子。特定目的4：确定前脑神经回路，特别是下丘脑的旁脑核是否与抑制SND对衰老大鼠的热应激的反应至关重要。电生理，中枢神经系统病变和灌注以及频域分析技术将用于完成这些研究。拟议的研究将首次推进以下假设：通过衰老来改变交感神经回电对热应激的反应的工作策略。