These studies are designed to address the hypothesis that mature canine coronary collaterals undergo active vasomotion in response to a variety of physiological and pharmacological stimuli. These changes in vascular tone may produce significant alterations in perfusion to collateral dependent myocardium. These studies are focuses on two general areas relevant to the coronary collateral circulation. The major thrust of these studies will be to examine adrenergic control of the coronary collateral circulation. These studies are relevant to cardiovascular physiology and cardiovascular medicine because the collateral circulation plays an extremely important role in delivering blood to ischemic myocardium. Changes in coronary collateral resistance secondary to adrenergic mechanisms may significantly alter perfusion to ischemic myocardium. Whether or not these """"""""newly"""""""" developed vessels contain adrenergic receptors and how they respond to adrenergic stimuli remains a largely unexplored issue. To perform these studies, we will employ four separate approaches: 1) biochemical ligand binding studies will be performed to determine receptor type and subtype in mature coronary collateral vessels. 2) The response of these vessels to a variety of adrenergic agonists and antagonists will be examined in isolated tissue baths. 3) The effect of alpha and beta agonists on coronary collateral resistance will be determined using an isolated blood perfused heart preparation. Using this preparation it should be possible to separate the effects of these agents on the coronary collateral vessels and on the resistance vessels downstream from the collaterals. 4) Using sonomicrometers implanted on mature coronary collaterals we will examine the effect of alpha and beta adrenergic agonists in a chronically instrumented conscious dog. These studies should allow us to examine changes in coronary collateral diameter secondary to adrenergic stimulation under physiologic conditions. A second major goal of these studies is to examine the effect of two commonly used pharmacologic agents (nitroglycerin and the calcium antagonists nifedipine) on coronary collateral smooth muscle and coronary collateral resistances. This work should provide important new information about regulation of coronary collateral flow.
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