SENESCENCE ALTERS SYMPATHETIC REGULATION TO HEAT STRESS

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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.