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.
| Helwig, Bryan G; Craig, Robin A; Fels, Richard J et al. (2008) Central nervous system administration of interleukin-6 produces splenic sympathoexcitation. Auton Neurosci 141:104-11 |
| Barman, Susan M; Kenney, Michael J (2007) Methods of analysis and physiological relevance of rhythms in sympathetic nerve discharge. Clin Exp Pharmacol Physiol 34:350-5 |
| Helwig, Bryan G; Musch, Timothy I; Craig, Robin A et al. (2007) Increased interleukin-6 receptor expression in the paraventricular nucleus of rats with heart failure. Am J Physiol Regul Integr Comp Physiol 292:R1165-73 |
| Ganta, Chanran K; Helwig, Bryan G; Blecha, Frank et al. (2006) Hypothermia-enhanced splenic cytokine gene expression is independent of the sympathetic nervous system. Am J Physiol Regul Integr Comp Physiol 291:R558-65 |
| Helwig, Bryan G; Parimi, Sujatha; Ganta, Chanran K et al. (2006) Aging alters regulation of visceral sympathetic nerve responses to acute hypothermia. Am J Physiol Regul Integr Comp Physiol 291:R573-9 |
| Ganta, Chanran K; Lu, Ning; Helwig, Bryan G et al. (2005) Central angiotensin II-enhanced splenic cytokine gene expression is mediated by the sympathetic nervous system. Am J Physiol Heart Circ Physiol 289:H1683-91 |
| Kenney, Michael J; Musch, Timothy I (2004) Senescence alters blood flow responses to acute heat stress. Am J Physiol Heart Circ Physiol 286:H1480-5 |
| Lu, Ning; Helwig, Bryan G; Fels, Richard J et al. (2004) Central Tempol alters basal sympathetic nerve discharge and attenuates sympathetic excitation to central ANG II. Am J Physiol Heart Circ Physiol 287:H2626-33 |
| Ganta, Chanran K; Blecha, Frank; Ganta, Roman R et al. (2004) Hyperthermia-enhanced splenic cytokine gene expression is mediated by the sympathetic nervous system. Physiol Genomics 19:175-83 |
| Kenney, M J; Weiss, M L; Haywood, J R (2003) The paraventricular nucleus: an important component of the central neurocircuitry regulating sympathetic nerve outflow. Acta Physiol Scand 177:7-15 |
Showing the most recent 10 out of 14 publications
