Effects of exercise training on endothelium-dependent vasodilation responses in porcine coronary arterioles exposed to chronic coronary occlusion : a dissertation /
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| Format: | Thesis Book |
| Language: | English |
| Published: |
[College Station, Tex.] :
[Texas A&M University System Health Science Center],
[2002]
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| Subjects: |
| Abstract: | ABSTRACT: Chronic coronary occlusion (CCO) impairs agonist-stimulated, nitric oxide (NO)-mediated vasodilation in porcine arterioles. These effects have been demonstrated to be reversed by long term exercise training (EX). It is hypothesized that EX enhances vasodilation responses to endothelium-dependent, NO-mediated agonists such as adenosine, adenosine diphosphate (ADP), and vascular endothelial growth factor (VEGF) in arterioles exposed to CCO. In order to address this hypothesis the proximal left circumflex coronary artery (LCx) of the female Yucatan mini-swine was surgically instrumented with an ameroid occluder to induce CCO; 8 weeks post-surgery the animals were randomized into 14 weeks of sedentary (SED) or EX (treadmill; 5 days/week) protocols. Coronary arterioles (<150 microm diameter) were isolated from collateral-dependent (LCx) and non-occluded (left anterior descending; LAD)-perfused myocardium of SED and EX animals. Vasodilation of pressurized (40 mmHg) arterioles was assessed using video microscopy and MacLab data acquisition. Vasodilation responses to adenosine and ADP were unaffected by CCO and/or EX in LAD and LCx arterioles. Vasodilation responses to human recombinant vascular endothelial growth factor (rhVEGF₁₆₅) were also unaffected by EX in nonoccluded LAD vessels. In contrast, EX markedly enhanced VEGF₁₆₅-induced vasodilation of collateral-dependent LCx arterioles (p<0.01; EX versus SED). Furthermore, VEGF₁₆₅-induced vasorelaxation of EX LCx arterioles exceeded that of EX or SED LAD arterioles (p=0.05). EX-induced enhanced vasodilation of LCx arterioles was abolished by inhibition of endothelial cell NO synthase (ecNOS) and tyrosine kinase activity. Vasorelaxation in response to VEGF₁₆₅ was reduced in all vessels by combined inhibition of NOS and cyclooxygenase. Importantly, this EX-induced enhanced vasodilation was not demonstrated in other isoforms of VEGF-A, specifically VEGF₁₂₁, and required the activation of a non-tyrosine kinase VEGF receptor, neuropilin-1. Therefore, these data indicate that EX enhances endothelial-dependent, NO-mediated responses to VEGF₁₆₅ in coronary arterioles under conditions of CCO via tyrosine kinase and non-tyrosine kinase signaling mechanisms. |
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| Item Description: | Vita. "Major Subject: Medical Sciences". "Submitted to the Graduate School of Biomedical Sciences of The Texas A&M University System Health Science Center in partial fulfillment for the requirements for the degree of Doctor of Philosophy December 2002." Approved as to style and content by: Janet L. Parker, Harris J. Granger, Michael D. Delp, Lih Kuo, Judy M. Muller-Delp. |
| Physical Description: | xii, 133 leaves : illustrations ; 28 cm + microfiche. |
| Bibliography: | Includes bibliographical references (leaves 115-133). |