CORONARY ARTERY ADRENERGIC RECEPTORS

Project Details

Description

Large coronary artery vasospasm can induce angina pectoris and even
myocardial infarction. The mechanisms responsible for coronary vasospasm
are not known, but potentially involve an increase in alpha adrenergic tone
or reduction in beta adrenergic tone. Most prior studies in this field
examined the coronary circulation as a whole by measuring coronary blood
flow and calculating coronary vascular resistance, and have not examined
the role of large coronary arteries, which is the major locus of coronary
vasospasm. Furthermore, the results of the few prior physiological studies
examining large coronary arteries have been conflicting and inconclusive.
The goal of this research proposal is to study large coronary arteries for
the first time with receptor ligand binding techniques and elucidate the
affinity (KD) and the number of receptors per mg protein of the Alpha1,
Alpha2, Beta1, and Beta2-adrenergic receptors in the normal large coronary
artery. By using bovine coronary arteries, which are relatively large and
the high affinity ligands 125I-pindolol for Beta-adrenergic studies,
125I-CP63,155 (analog of prazosin) for Alpha1-adrenergic studies, and
3H-rauwolscine for Alpha2-adrenergic studies, the study of coronary
arteries will be feasible, despite the relatively small amounts of protein
and small numbers of receptors in those vessels. An additional unique
feature of this research proposal is to correlate the findings from the
biochemical studies with physiological studies in conscious, chronically
instrumented calves. Specifically, Alpha and Beta-adrenergic agonists and
antagonists will be delivered intracoronary (to avoid systemic effects) to
conscious calves instrumented for direct and continuous measurement of left
circumflex coronary artery diameter and blood flow. This research proposal
represents the first identification and quantitation of adrenergic
receptors in coronary arteries utilizing receptor ligand binding techniques
and the first correlation of these measurements with physiological
measurements of responses of large coronary arterial dimensions to
adrenergic agonists and antagonists. The results of these studies will
provide basic information relating to potential adrenergic mechanisms
involved in coronary artery spasm.
StatusFinished
Effective start/end date12/31/8912/31/89

Funding

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

ASJC

  • Cardiology and Cardiovascular Medicine

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