Single bouts of exercise in hypertensive subjects can lead to a long-lasting decrease in sympathetic nerve activity that results in a post-exercise hypotension (PEH) which can normalize high blood pressure. PEH requires an intact baroreflex system; but, the gain of the system in regulating sympathetic nerve activity is reduced. Although the potential therapeutic benefits are appreciated, the mechanisms whereby exercise in hypertensive subjects leads to a persistent lowering of high blood pressure through a decreased central sympathetic output and at the same time to a reduced gain of baroreflex control of sympathetic output are unknown. The goal of this proposal is to resolve those mechanisms. Our data suggest that PEH and the reduced gain are mediated by exercise-induced changes in the central baroreflex network, specifically, in the nucleus tractus solitarius (NTS) where baroreceptor signals are first processed and at sympathetic cardiovascular neurons in the rostral ventrolateral medulla (RVLM), the sympathetic output pathway. We pose two Specific Hypotheses: 1. The underpinning of PEH is a decrease in the impulse activity of RVLM sympathetic cardiovascular neurons, a decrease mediated by: a) a tonic increase in the impulse activity of baroreceptor NTS neurons (increasing the tonic level of GABA release at GABAA receptors (GABAA-Rs) on RVLM neurons), and b) an upregulation of RVLM GABAA-RS (amplifying the efficacy of the tonic GABA inhibitory input to the RVLM neurons). 2. The reduced baroreflex gain originates in the NTS (such that for a given change in blood pressure and baroreceptor input, the corresponding change in NTS neuronal output (and hence dynamic GABA release in the RVLM) is reduced. The hypotheses will be tested by four aims using extracellular recording of NTS and RVLM neuronal activity in the central baroreflex network in vivo; patch-clamping in medullary slices containing NTS and RVLM neurons in the central network; and real-time RT-PCR from NTS and RVLM micropunches in spontaneously hypertensive rats (SHR).
Aims 1 -2 will resolve GABA mechanisms in the RVLM (GABA release and GABAA-R gene expression) mediating PEH and Aims 3-4 will address pre- and postsynaptic mechanisms in the NTS in mediating PEH and the reduced gain.
| Chen, Chao-Yin; Bonham, Ann C (2010) Postexercise hypotension: central mechanisms. Exerc Sport Sci Rev 38:122-7 |
| Chen, Chao-Yin; Bechtold, Andrea G; Tabor, Jocelyn et al. (2009) Exercise reduces GABA synaptic input onto nucleus tractus solitarii baroreceptor second-order neurons via NK1 receptor internalization in spontaneously hypertensive rats. J Neurosci 29:2754-61 |
| Chen, Chao-Yin; Munch, Paul A; Quail, Anthony W et al. (2002) Postexercise hypotension in conscious SHR is attenuated by blockade of substance P receptors in NTS. Am J Physiol Heart Circ Physiol 283:H1856-62 |
| Kajekar, Radhika; Chen, Chao-Yin; Mutoh, Tatsushi et al. (2002) GABA(A) receptor activation at medullary sympathetic neurons contributes to postexercise hypotension. Am J Physiol Heart Circ Physiol 282:H1615-24 |
