Exercise training-induced adaptations in mediators of sustained endothelium-dependent coronary artery relaxation in a porcine model of ischemic heart disease.
OBJECTIVE
The aim of this study was to test the hypothesis that exercise training enhances sustained relaxation to persistent endothelium-dependent vasodilator exposure via increased nitric oxide contribution in small coronary arteries of control and ischemic hearts.


METHODS
Yucatan swine were designated to a control group or a group in which an ameroid constrictor was placed around the proximal LCX. Subsequently, pigs from both groups were assigned to exercise (five days/week; 16 weeks) or SED regimens. Coronary arteries (~100-350 μm) were isolated from control pigs and from both nonoccluded and collateral-dependent regions of chronically-occluded hearts.


RESULTS
In arteries from control pigs, training significantly enhanced relaxation responses to increasing concentrations of bradykinin (10(-10) -10(-7) M) and sustained relaxation to a single bradykinin concentration (30 nM), which were abolished by NOS inhibition. Training also significantly prolonged bradykinin-mediated relaxation in collateral-dependent arteries of occluded pigs, which was associated with more persistent increases in endothelial cellular Ca(2+) levels, and reversed with NOS inhibition. Protein levels for eNOS and p-eNOS-(Ser1179), but not caveolin-1, Hsp90, or Akt, were significantly increased with occlusion, independent of training state.


CONCLUSIONS
Exercise training enhances sustained relaxation to endothelium-dependent agonist stimulation in small arteries of control and ischemic hearts by enhanced nitric oxide contribution and endothelial Ca(2+) responses.
Michael E. DeBakey Institute for Comparative Cardiovascular Science and Biomedical Devices, Texas A&M University, College Station, Texas, USA; Department of Physiology and Pharmacology, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, Texas, USA.
Cristine L
CL
Heaps
Juan Carlos
JC
Robles
Vandana
V
Sarin
Mildred L
ML
Mattox
Janet L
JL
Parker
D000222:Adaptation, Physiological; D000818:Animals; D001920:Bradykinin / Q000378:metabolism; D051242:Caveolin 1 / Q000378:metabolism; D003331:Coronary Vessels / Q000378:metabolism / Q000503:physiopathology*; D004730:Endothelium, Vascular / Q000378:metabolism / Q000503:physiopathology*; D018841:HSP90 Heat-Shock Proteins / Q000378:metabolism; D017202:Myocardial Ischemia / Q000378:metabolism / Q000503:physiopathology*; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D010805:Physical Conditioning, Animal; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D013552:Swine; D013556:Swine, Miniature; D014664:Vasodilation
D051242:Caveolin 1; D018841:HSP90 Heat-Shock Proteins; D052250:Nitric Oxide Synthase Type III; D051057:Proto-Oncogene Proteins c-akt; D001920:Bradykinin
bradykinin; calcium; collateral; coronary occlusion; ischemic heart disease; isometric tension