This study tested the hypothesis that an α-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 submaximal 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 specificα1-adrenergic receptor antagonist prazosin (1μg·kg-1·min-1) was infused into the circumflex artery during exercise. Removal of an α1-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 α1-blockade was associated with significant increases in both regional and global left ventricular contractile function. These studies indicate that a uniformly distributed transmural coronary α1-constrictor tone increases in magnitude with increasing levels of exercise intensity and, as a result, imposes a significant limitation on myocardial function.
Department of Physiology, University of North Texas Health Science Center at Fort Worth, Fort Worth, TX 76107
Submitted for publication August 1994.
Accepted for publication September 1995.
The authors are grateful to Mrs. Charlene Ghaedi for her secretarial assistance and to Ms. Linda Howard for her expert technical assistance. We wish to acknowledge the generosity of Pfizer, Inc. for providing Prazosin HCl. These studies were supported by NIH grants HL-34172 and HL-29232 and a Grant-in-Aid from the Texas Affiliate of the American Heart Association.
This research was performed as partial fulfillment of the dissertation requirements for the Ph.D. degree for Jeffrey M. Dodd-o, M.D.
Address for correspondence: Patricia A. Gwirtz, Ph.D., Professor, Department of Physiology, University of North Texas Health Science Center, 3500 Camp Bowie Boulevard, Fort Worth, TX 76107-2699; E-mail:firstname.lastname@example.org.