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) decrease in muscarinic receptor density in
left ventricular failures, 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
receoptor and two dimensional electrophoresis to identify the
molecular weight and isoelectric point of the beta-adrenergic
receoptor in theleft 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 hyeprtension, 2) the progression of changes in high
affinity beta-adrenergic and muscarinic agonist binding,
muscarinic density and modulation of adenylate cyclase activity
and functions as left hypertrophy progresses from mild to severe
left ventricular hypertrophy, 3) changes in beta2-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 levle,
of one of the most important problems in clinical cardiology, i.e.,
left ventricular hypertrophy and heart failure.
StatusFinished
Effective start/end date12/31/898/31/98

Funding

  • National Heart, Lung, and Blood Institute
  • National Heart, Lung, and Blood Institute
  • National Heart, Lung, and Blood Institute
  • National Heart, Lung, and Blood Institute
  • National Heart, Lung, and Blood Institute
  • National Heart, Lung, and Blood Institute
  • National Heart, Lung, and Blood Institute

ASJC

  • Medicine(all)
  • Cardiology and Cardiovascular Medicine
  • Physiology

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