Grants and Contracts Details
Description
The goal of this fellowship is to identify the role of TRPV1 channels on sodium osmosensitive neurons of the
organum vasculosum of the lamina terminalis (OVLT) and its descending hypothalamic pathways in the control
of sympathetic nerve activity and blood pressure in a model of rat salt-sensitive hypertension. My preliminary
data indicate that electrical stimulation of OVLT neurons produces a sympathetically-mediated increase in
arterial blood pressure that depends on the hypothalamic paraventricular nucleus (PVH). Our working
hypothesis is that increases in plasma sodium (Le. hyperosmotic stimuli) activate TRPV1 channels to increase
the tonic activity of OVLT neurons. Activated OVLT neurons projecting to the PVH excite
sympathetic-regulatory within the PVH through local activation of excitatory amino acid (EM) or angiotensin
II-type 1A receptors. In turn, PVH sympathetic neurons increase sympathetic outflow and arterial blood
pressure through mono- and poly-synaptic pathways through the brainstem and spinal cord. Specific aim #1
will identify the synaptic mechanisms within the PVH that mediate sympathetic nerve activity and arterial blood
pressure responses produced by OVLT stimulation. Specific aim #2 will identify the neurochemical phenotype
of OVLT neurons projecting to the PVH responsive to changes in plasma sodium. Specific Aim #3 will identify
the contribution of TRPV1 channel activation within the OVLT to elevated sympathetic nerve activity and
arterial blood pressure in salt-sensitive hypertension (DOCA salt hypertensive rats). Experiments will involve
identification of the specific neural pathways, neurotransmitters, receptors, and cellular mechanisms that
contribute to salt-sensitive hypertension via increases in sympathetic outflow from the brain. This research
encompasses the mission statement of the American Heart Association concerning the reduction in "disability
and death from cardiovascular diseases and stroke". Investigation into the role of the central nervous system
and its relationship with salt in the development of hypertension represents a poorly understood area of public
health. The response of the brain to salt and related mechanisms involved in the control of blood pressure
must be determined. Insight gained in this area will provide the framework for the development of specific
drugs acting on the central nervous system for the treatment of salt-sensitive hypertension in humans.
Status | Finished |
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Effective start/end date | 7/1/07 → 9/13/07 |
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