Effects of nonselective and selective alpha 1-adrenergic blockade on coronary blood flow during exercise

Abstract

This study was made to evaluate the relative importance of alpha 1- and alpha 2-adrenergic vasoconstrictor influences in opposing the increase in coronary blood flow that occurs during exercise. The effects of selective alpha 1-adrenergic blockade with prazosin were compared with nonselective alpha-adrenergic blockade with phentolamine on coronary hemodynamics during exercise in chronically instrumented dogs. During control conditions, graded treadmill exercise resulted in progressive increases of myocardial oxygen consumption; this was associated with increased coronary blood flow as well as with increased myocardial oxygen extraction. Although prazosin and phentolamine caused similar reductions of arterial pressure, phentolamine increased heart rate, myocardial oxygen consumption, and coronary blood flow at equivalent exercise levels, and prazosin did not significantly alter these variables. These effects of phentolamine appeared to result from blockade of presynaptic alpha 2-adrenergic receptors, which normally modulate norepinephrine release, that resulted in increased sympathetic effects on the heart. However, at comparable levels of myocardial oxygen consumption, prazosin and phentolamine resulted in similar significant increases of coronary venous PO2 and decreases of coronary vascular resistance. These data support a modest role for alpha 1-adrenergic coronary vasoconstriction during exercise but fail to document an additional role for postsynaptic alpha 2-adrenergic coronary vasoconstriction during exercise.