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Exercise Training‐Induced Adaptations in Mediators of Sustained Endothelium‐Dependent Coronary Artery Relaxation in a Porcine Model of Ischemic Heart Disease
Author(s) -
Heaps Cristine L.,
Robles Juan Carlos,
Sarin Vandana,
Mattox Mildred L.,
Parker Janet L.
Publication year - 2014
Publication title -
microcirculation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.793
H-Index - 83
eISSN - 1549-8719
pISSN - 1073-9688
DOI - 10.1111/micc.12116
Subject(s) - bradykinin , enos , nitric oxide , vasodilation , medicine , endothelium , cardiology , coronary arteries , nitric oxide synthase , endocrinology , artery , receptor
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.