EXPERIMENTAL NEUROGENIC HYPERTENSION PROGRAM

  • Wahlestedt, Claes R (PI)
  • Iadecola, Costantino (PI)
  • Anrather, Josef (PI)
  • Golanov, Eugene (PI)
  • Feinstein, Douglas (PI)
  • Milner, Teresa (PI)
  • Pickel, Virginia (PI)
  • Miao-Kun, S.U.N. (PI)
  • Tucker, Lewis (PI)
  • Meeley, Mary (PI)
  • Milner, Teresa (PI)
  • Ruggiero, David (PI)
  • Pickel, Virginia (PI)
  • Reis, Donald (PI)

Project: Research project

Description

The proposal represents a continuation of a Program in Experimental
Neurogenic Hypertension. It delineates a series of fundamental
multidisciplinary studies into the neurobiology of the central control of
portions of the autonomic nervous system regulating arterial pressure. The
broad objectives of this study are: (a) to map by neuroanatomical
techniques using transport of tracers, functional mapping with
2-deoxyglucose and immunocytochemical methods both by light and electron
microscopy the pathways, neurotransmitters and synaptic interactions of
pathways in the brain subserving cardiovascular control, including those of
the nucleus tractus solitarii (NTS), rostral regions of the medulla
including those containing C1 adrenergic neurons, and portions of the
anterior hypothalamus; (b) to examine the manner by which the brain
regulates cerebral blood flow and metabolism and, in particular, the
adrenal and adrenal-independent mechanisms eliciting global metabolic
changes elicited from the medullary reticular formation; (c) to determine
by light and electron miscroscopy, by electrophysiology, including
iontophoretic techniques, the synaptic interactions and transmitter
characteristics of pathways between the NTS, the C1 area of the rostral
ventrolateral medulla and the sympathetic preganglionic neurons of the
spinal cord, regions critically involved in the tonic and reflex control of
blood pressure; (d) to characterize by neurochemical and autoradiographic
procedures the neurotransmitters and their receptors residing in the
critical medullary cardiovascular sites, the NTS and C1 area, with
identification, if possible, of new transmitter agents; (e) to characterize
the role of cholinergic mechanisms in brainstem cardiovascular control; (f)
to identify the pathways in the brain which subserve the expression of the
elevations of arterial pressure associated with emotional conditioning (the
conditioned emotional response), and to trace the pathways through which
the conditioned auditory signals acquire their emotional coloration; (g) to
isolate the genes responsible for the biosynthesis of catecholamine
biosynthetic enzymes, tyrosine hydroxylase (TH), dopamine-B-hydroxylase
(DBH) and phenylethanolamine N-methyltransferase (PNMT); (h) to
characterize the steps in transcriptional and translational control of the
expression of adrenal medullary catecholamine biosynthetic enzymes; (i) to
determine the timing and regulation of the differentiation of cholinergic
elements of the autonomic nervous system by use of biochemical,
immunocytochemical and genetic analysis in vivo and in vitro in
relationship to the expression or suppression of catecholamine phenotypes.
StatusFinished
Effective start/end date5/1/766/30/09

Funding

  • National Institutes of Health

Fingerprint

Solitary Nucleus
Autonomic Nervous System
Catecholamines
Cerebrovascular Circulation
Arterial Pressure
Phenylethanolamine N-Methyltransferase
Light
Adrenergic Neurons
Neurotransmitter Receptor
Reticular Formation
Neurobiology
Electrophysiology
Deoxyglucose
Brain
Tyrosine 3-Monooxygenase
Enzymes
Mixed Function Oxygenases
Cholinergic Agents
Hypothalamus
Brain Stem

ASJC

  • Medicine(all)