The major specific aims of this research are: (1) to develop and validate direct methods of biochemical analysis of beta adrenergic receptor characteristics in cardiac tissue and in skeletal muscle that are applicable to studies of living human and animal subjects; (2) to employ these methods to clarify the role of cardiac and skeletal muscle beta adrenergic receptor characteristics as determinants of normal cardiovascular and exercise physiology; and (3) to clarify the role of altered cardiac beta adrenergic receptors in the pathophysiology of human cardiovascular disease, particularly of congestive heart failure. Using cardiac tissue obtained by transvenous endomyocardial biopsy in dogs, we shall assess beta receptor characteristics, their correlation with physiologic responsiveness to beta adrenergic agonists, the kinetics of their regulation by various stimuli, and their correlation with beta receptor characteristics of other tissues. Subsequent human studies will analyze the relationships between biochemical parameters of cardiac beta adrenergic receptors and selected clinical characteristics of subjects undergoing cardiac catheterization or cardiac surgery. We shall also assess beta adrenergic receptor characteristics in skeletal muscle samples obtained by percutaneous needle biopsy from both dogs and humans, their regulation by various stimuli, their role in normal exercise physiology, and their correlation with beta adrenergic receptor characteristics of cardiac tissue and leukocytes. This research has considerable potential to fill existing gaps in knowledge of adrenergic receptor biology, of exercise physiology, and of the pathophysiologic role of altered cardiac adrenergic receptor properties in human cardiac disease. It is also conceivable that the techniques to developed for analysis of human cardiac beta adrenergic receptors could become clinical aids in the diagnosis and therapeutic management of cardiomyopathies.
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| Williams, R S (1986) Mitochondrial gene expression in mammalian striated muscle. Evidence that variation in gene dosage is the major regulatory event. J Biol Chem 261:12390-4 |
