AUTONOMIC RECEPTOR FUNCTION IN LV HYPERTROPHY &FAILURE

Project Details

Description

The principal investigator and her colleagues have identified
several alterations in beta-adrenergic and muscarinic receptor
function and adenylate cyclase activity in left ventricular
hypertrophy and failure. These include: 1) decreases in the beta-
adrenergic receptor high affinity agonist binding sites in left
ventricular failure, 2) decreases in muscarinic receptor density in
left ventricular failure, 3) decreased adenylate cyclase activity in
left ventricular failure, and 4) decreased muscarinic inhibition of
adenylate cyclase activity in left ventricular failure. The first
goal of this application is to delineate the biochemical
mechanisms underlying these alterations. This will be
accomplished by 1) identifying a potentially altered receptor-
protein by photoaffinity labelling of the beta-adrenergic receptor
and two dimensional electrophoresis to identify the molecular
weight and isoelectric point of the beta-adrenergic receptor in
the left ventricular of animals with left ventricular hypertrophy
and failure, 2) to examine guanine nucleotide regulatory protein
function in left ventricular hypertrophy and failure. The second
goal of this application is to define the time course and generality
of the defects. This will be accomplished by examining 1) another
model of left ventricular hypertrophy, i.e. renal hypertension, 2)
the progression of changes in high affinity beta-adrenergic and
muscarinic agonist binding, muscarinic density and modulation of
adenylate cyclase activity and function as left ventricular
hypertrophy progresses from mild to severe left ventricular
hypertrophy, 3) changes in adrenergic receptors in normal, left
ventricular hypertrophy, and failure, 4) changes in alpha-
adrenergic receptors. The third goal of the present application is
to determine the selectivity of defects for cardiac muscle by
using a purified sarcolemma preparation and finally the study of
isolated myocytes to remove most of the non-myocyte tissue
before preparing membranes. It is proposed that these studies
will enhance our understanding at the cellular level, of one of the
most important problems in clinical cardiology, i.e., left
ventricular hypertrophy and heart failure.
StatusFinished
Effective start/end date8/1/877/31/92

Funding

  • National Institutes of Health: $66,566.00
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health

ASJC

  • Medicine(all)

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