Chronic occlusion, exercise training, nitric oxide, and reactive oxygen species : a dissertation /
ABSTRACT : Previous studies have reported that endothelial nitric oxide synthase contributes to improved vascular function after exercise training. The major purpose of the studies reported in this dissertation was to determine the effect of exercise training on the nitric oxide and superoxide /H₂O₂...
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| Format: | Thesis Book |
| Language: | English |
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[College Station, Tex.] :
[Texas A&M University System Health Science Center],
[2011]
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| Summary: | ABSTRACT : Previous studies have reported that endothelial nitric oxide synthase contributes to improved vascular function after exercise training. The major purpose of the studies reported in this dissertation was to determine the effect of exercise training on the nitric oxide and superoxide /H₂O₂ signaling pathways in coronary arterioles from nonoccluded and collateral-dependent regions of chronically occluded pig hearts. In this series of studies, we tested two hypotheses: 1) exercise training enhances endothelial function via endothelium-derived vasodilators, nitric oxide and H₂O₂, in the underlying setting of chronic coronary artery occlusion; and 2) exercise training enhances H₂O₂-stimulated BK[Ca] channel to endothelium-dependent dilation of coronary arterioles from nonoccluded and collateral-dependent regions of chronically occluded pig hearts. To test these hypotheses, an ameroid constrictor was placed around the proximal left circumflex coronary artery to induce gradual occlusion in Yucatan miniature swine. Eight weeks postoperatively, pigs were randomly assigned to sedentary (pen-confined) or exercise training (treadmill run; 5 days/wk; 14 wk) regimens. Coronary arterioles were isolated from pig hearts for determination of endothelium-dependent dilation or biochemical analyses. Results from these studies suggest that: 1) exercise training significantly enhanced concentration-dependent, bradykinin-mediated dilation in collateral-dependent arterioles compared with sedentary pigs; 2) exercise-enhanced bradykinin-mediated dilation was attributed to nitric oxide at lower bradykinin concentrations and H₂O₂ at high bradykinin concentrations. 3) Total eNOS and p-eNOS (Ser1179) protein levels were significantly increased in arterioles from collateral-dependent compared with the nonoccluded region, independent of exercise; 4) The BK[Ca] channel blocker, iberiotoxin, alone or in combination with the H₂O₂ scavenger, polyethylene glycol catalase, similarly reversed exercise training-enhanced dilation in collateral-dependent arterioles; 5) Iberiotoxin-sensitive whole-cell K⁺ currents were not different between smooth muscle cells of nonoccluded and collateral-dependent arterioles of sedentary and exercise trained groups, indicating that BK[Ca] channel currents were not altered by occlusion or exercise training; and 6) The NADPH oxidase inhibitor, apocynin, significantly attenuated bradykinin-mediated dilation in nonoccluded and collateral-dependent coronary arterioles of exercise trained pigs but not sedentary pigs. However, neither exercise nor occlusion significantly altered arteriolar superoxide levels or superoxide dismutase isoform protein levels or enzyme activity. These data provide evidence that in addition to nitric oxide, the superoxide/H₂O₂ signaling pathway contributes to exercise training-enhanced endothelium-mediated dilation through increased BK[Ca] channel activation in collateral-dependent coronary arterioles. |
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| Item Description: | Vita. "Major Subject: Medical Sciences." "Submitted to the Office of Research and Graduate Studies of The Texas A&M University System Health Science Center in partial fulfillment of the requirements for the degree of Doctor of Philosophy August 2011." Approved as to style an content by: Cristine L. Heaps, Cynthia J. Meininger, Harris J. Granger, Janet L. Parker, Emily Wilson. |
| Physical Description: | xviii, 129 leaves : charts ; 29 cm. |
| Bibliography: | Includes bibliographical references (leaves 110-128). |