The role of alpha 1- and alpha 2-adrenergic receptors in mediation of coronary vasoconstriction in hypoperfused ischemic myocardium during exercise.

This study was carried out to test the hypothesis that adrenergic coronary vasoconstriction limits blood flow to hypoperfused regions of myocardium during exercise. The vasoconstrictor influence of alpha-adrenergic receptor subtypes was assessed by use of selective adrenergic blocking agents. Dogs chronically instrumented with a circumflex coronary artery hydraulic occluder and an intra-arterial catheter underwent treadmill exercise in the presence of a coronary stenosis that decreased distal perfusion pressure to 40 mm Hg. Myocardial blood flow was measured with radioactive microspheres (15 microns) before and during selective alpha 1- or alpha 2-adrenergic receptor blockade produced by intracoronary infusion of prazosin (1 microgram/kg/min x 10 min) or idazoxan (1 microgram/kg/min x 10 min), respectively. Coronary perfusion pressure was held equal before and during receptor blockade with the hydraulic occluder. Compared with control exercise, subendocardial blood flow increased during alpha 1-receptor blockade with prazosin from 0.60 +/- 0.14 to 1.12 +/- 0.17 ml/min/g (p less than 0.05), and mean transmural flow increased from 1.07 +/- 0.19 to 1.60 +/- 0.22 ml/min/g (p less than 0.05). In contrast, subendocardial and mean transmural blood flow were not different from control during selective alpha 2-adrenergic receptor blockade with idazoxan (0.48 +/- 0.10 vs. 0.67 +/- 0.14 ml/min/g, p = 0.33, and 0.82 +/- 0.15 vs. 1.02 +/- 0.20 ml/min/g, p = 0.45, respectively). These data indicate that even in the presence of a coronary stenosis that causes substantial myocardial underperfusion during exercise, residual coronary vasoconstrictor tone is present in ischemic myocardium, and this vasoconstriction is mediated predominantly by the alpha 1-adrenergic receptor.