Coronary ??1-adrenergic constrictor tone varies with intensity of exercise

This study tested the hypothesis that an alpha-adrenergic coronary constrictor tone increases with the intensity of exercise and imposes a limitation on transmural myocardial blood flow and contractile function during strenuous levels of exercise. Nine (9) dogs were chronically instrumented to measure left circumflex blood flow (CBF), global myocardial contractile function (dP/dtmax), and regional myocardial contractile function (maximal rate of segmental shortening, dL/dtmax). The dogs were subjected to a graded sub-maximal exercise test with increasing workloads encompassing 4.8 kph and 6.4 kph, 0, 4, 8, 12, and 16% incline. On separate days, either vehicle (sterile water) or the specific alpha 1-adrenergic receptor antagonist prazosin (1 microgram.kg-1.min-1) was infused into the circumflex artery during exercise. Removal of an alpha 1-receptor mediated coronary constrictor tone resulted in a 15 +/- 7%, 24 +/- 9%, and 35 +/- 10% greater increase in CBF compared with vehicle at the three most strenuous levels of exercise, respectively. Regional left ventricular blood flow was measured using labeled microspheres in four (4) additional dogs. Endocardial and epicardial blood flow increased equally by 16% during exercise after prazosin, such that the endocardial/epicardial flow ratio did not change. The augmentation in CBF after alpha 1-blockade was associated with significant increases in both regional and global left ventricular contractile function. These studies indicate that a uniformly distributed transmural coronary alpha 1-constrictor tone increases in magnitude with increasing levels of exercise intensity and, as a result, imposes a significant limitation on myocardial function.