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.
|Vatner, D E; Vatner, S F; Fujii, A M et al. (1985) Loss of high affinity cardiac beta adrenergic receptors in dogs with heart failure. J Clin Invest 76:2259-64|