title: Exercise training enhances multiple mechanisms of relaxation in coronary arteries from ischemic hearts.
abstract: Exercise training of coronary artery disease patients is of considerable interest, since it has been shown to improve vascular function and, thereby, enhance blood flow into compromised myocardial regions. However, the mechanisms underlying exercise-induced improvements in vascular function have not been fully elucidated. We tested the hypothesis that exercise training increases the contribution of multiple mediators to endothelium-dependent relaxation of coronary arteries in the underlying setting of chronic coronary artery occlusion. To induce gradual occlusion, an ameroid constrictor was placed around the proximal left circumflex coronary artery in Yucatan miniature swine. At 8 wk postoperatively, pigs were randomly assigned to sedentary or exercise (treadmill, 5 days/wk) regimens for 14 wk. Exercise training significantly enhanced the contribution of nitric oxide, prostanoids, and large-conductance Ca(2+)-dependent K(+) (BKCa) channels to endothelium-dependent, bradykinin-mediated relaxation in nonoccluded and collateral-dependent arteries. Combined nitric oxide synthase, prostanoid, and BKCa channel inhibition ablated the enhanced relaxation associated with exercise training. Exercise training significantly increased nitric oxide levels in response to bradykinin in endothelial cells isolated from nonoccluded and collateral-dependent arteries. Bradykinin treatment significantly increased PGI2 levels in all artery treatment groups and tended to be further enhanced after nitric oxide synthase inhibition in exercise-trained pigs. No differences were found in whole cell BKCa channel currents, BKCa channel protein levels, or arterial cyclic nucleotide levels. Although redundant, upregulation of parallel vasodilator pathways appears to contribute to enhanced endothelium-dependent relaxation, potentially providing a more refined control of blood flow after exercise training.
authors.affiliation: Michael E. DeBakey Institute for Comparative Cardiovascular Science and Biomedical Devices, College of Veterinary Medicine and Biomedical Sciences, Texas A & M University, College Station, Texas; and.
authors.forename: Rachel R
authors.initials: RR
authors.lastname: Deer
authors.forename: Cristine L
authors.initials: CL
authors.lastname: Heaps
mesh_terms: D000818:Animals; D001920:Bradykinin / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D003331:Coronary Vessels / Q000378:metabolism / Q000503:physiopathology*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000378:metabolism / Q000503:physiopathology*; D011464:Epoprostenol / Q000378:metabolism; D005081:Exercise Therapy; D005260:Female; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000378:metabolism; D017202:Myocardial Ischemia / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy*; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D057185:Sedentary Behavior; D013552:Swine; D013556:Swine, Miniature; D013997:Time Factors; D014664:Vasodilation
chemical_list: D002121:Calcium Channel Blockers; D016861:Cyclooxygenase Inhibitors; D051036:Large-Conductance Calcium-Activated Potassium Channels; D009569:Nitric Oxide; D011464:Epoprostenol; D019001:Nitric Oxide Synthase; D001920:Bradykinin
keywords: chronic coronary artery occlusion; endothelium; exercise