A disfunção endotelial atua tanto na aterogênese como na precipitação das síndromes coronárias agudas. A redução da biodisponibilidadedo óxido nítrico é expressão de endotélio disfuncional. O mecanismo desta redução não está elucidado. A presença de disfunção endotelialfoi correlacionada com fatores de risco (FR), nitrato sanguíneo e fatores genéticos (polimorfismo da óxido nítrico sintase endotelial, fibrinogênio e PAI-1) em um grupo de 128 pacientes com infarto do miocárdio (IAM) e idade = 40 anos, submetidos a ultra-som de artéria braquial. Os resultados foram comparados com um grupo jovens saudáveis. Verificou-se que pacientes jovens com IAM apresentavam disfunção endotelial em associação com FR, alterações bioquímicas e níveis aumentados de nitrato, porém sem alterações genéticas / The endothelial dysfunction plays an important roll in the atherogenesis and precipitation of acute coronary syndromes. The reduction of bioavailability of the nitric oxide is the expression of endothelial dysfunction. The exact mechanism of this reduction is not yet well explained. In order to evaluate the presence of endothelial dysfunction and correlation with risk factors (FR), nitrate blood levels and genetic factors (endothelial nitric oxide synthease polymorphism, fibrinogen and PAI-1) a 128 myocardial infarction patients group with age = 40 year was studied, and underwent a brachial artery ultra-sound. The results were compared with a group of young health individuals. The study found that the young patients with myocardial infarctions showed endothelial dysfunction with associated risks factors, biochemical changes and higher levels of nitrate, although without any significant genetic changes

Dong Yingying. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2005. / Includes bibliographical references (leaves 99-125). / Abstracts in English and Chinese. / Declaration --- p.i / Acknowledgement --- p.ii / Publication list --- p.iii / Abstract (English) --- p.ix / Abstract (Chinese) --- p.xii / Abbreviations --- p.xiv / List of figures / tables --- p.xvi / Chapter Chapter 1. --- General Introduction / Chapter 1.1 --- The role of endothelium in regulating vascular tone --- p.1 / Chapter 1.1.1 --- Nitric oxide (NO) --- p.2 / Chapter 1.1.2 --- Endothelium-derived hyperpolarizing factor (EDHF) --- p.7 / Chapter 1.1.3 --- Prostacyclin (PGI2) --- p.20 / Chapter 1.2 --- EDHF-mediated endothelial function in coronary circulation --- p.22 / Chapter 1.2.1 --- Role of EDHF in coronary microarteries --- p.23 / Chapter 1.2.2 --- Role of EDHF in cardiac veins --- p.24 / Chapter 1.3 --- Effect of ischemia-reperfusion on endothelial function in coronary circulation --- p.25 / Chapter 1.3.1 --- Ischemia-reperfusion injury --- p.26 / Chapter 1.3.2 --- Effect of ischemia-reperfusion on endothelial function in coronary microarteries --- p.28 / Chapter 1.3.3 --- Effect of ischemia-reperfusion on endothelial function in cardiac veins --- p.29 / Chapter 1.4 --- Alteration of endothelial function during cardiac surgery / Chapter 1.4.1 --- Cardioplegia and organ preservation solutions --- p.31 / Chapter 1.4.2 --- Combined effects of hypoxia-reoxygenation and ST solution on endothelial function in coronary microarteries/cardiac veins --- p.34 / Chapter 1.4.3 --- Effect of nicorandil on endothelial function --- p.34 / Chapter Chapter 2. --- Materials and Methods --- p.37 / Chapter 2.1 --- Isometric force study in micro arteries/veins --- p.37 / Chapter 2.1.1 --- Preparation of vessels --- p.37 / Chapter 2.1.1.1 --- Preparation of porcine coronary microarteries --- p.37 / Chapter 2.1.1.2 --- Preparation of porcine cardiac veins --- p.37 / Chapter 2.1.2 --- Technique of setting up --- p.39 / Chapter 2.1.2.1 --- Mounting of microvessels --- p.39 / Chapter 2.1.2.2 --- Normalization procedure for microvessels --- p.39 / Chapter 2.1.3 --- EDHF-mediated vasorelaxation --- p.40 / Chapter 2.1.3.1 --- Precontraction and stimuli of EDHF --- p.40 / Chapter 2.1.3.2. --- “Truéحresponse of EDHF --- p.40 / Chapter 2.1.4 --- Data acquisition and analysis --- p.41 / Chapter 2.2 --- Hypoxia and reoxygenation --- p.41 / Chapter 2.2.1 --- Calibration of 02-special electrode --- p.41 / Chapter 2.2.2 --- Measurement of --- p.02 / Chapter 2.3 --- Statistical analysis --- p.42 / Chapter 2.4 --- Chemicals --- p.43 / Chapter Chapter 3. --- Hypoxia-Reoxygenation in Coronary Microarteries: Combined Effect with St Thomas Cardioplegia and Temperature on the Endothelium- derived Hyperpolarizing Factor and Protective Effect of Nicorandil --- p.44 / Chapter 3.1 --- Abstract --- p.44 / Chapter 3.2 --- Introduction --- p.45 / Chapter 3.3 --- Experimental design and analysis --- p.47 / Chapter 3.3.1 --- Vessel Preparation --- p.47 / Chapter 3.3.2 --- Normalization --- p.48 / Chapter 3.3.3 --- Hypoxia --- p.48 / Chapter 3.3.4 --- Effect of H-R on EDHF-mediated relaxation in coronary microarteries --- p.49 / Chapter 3.3.5 --- Combined effects ofH-R and ST solution on EDHF-mediated relaxation in coronary microarteries --- p.49 / Chapter 3.3.6 --- Effect of addition of nicorandil Krebs or ST solution under H-R on EDHF-mediated relaxation in coronary microarteries --- p.49 / Chapter 3.3.7 --- Data analysis --- p.50 / Chapter 3.4 --- Results --- p.51 / Chapter 3.4.1 --- Resting force --- p.51 / Chapter 3.4.2 --- U46619-induced contraction force --- p.51 / Chapter 3.4.3 --- Partial pressure of oxygen in hypoxia --- p.51 / Chapter 3.4.4 --- EDHF-mediated relaxation in coronary microarteries --- p.51 / Chapter 3.4.4.1 --- Effect of H-R --- p.51 / Chapter 3.4.4.2 --- Combined effects ofH-R and ST solution on EDHF-mediated relaxation --- p.52 / Chapter 3.4.4.3 --- Effects of addition of nicorandil to Krebs or ST solution under H-R on EDHF-mediated relaxation --- p.52 / Chapter 3.5 --- Discussion --- p.53 / Chapter 3.5.1 --- EDHF-mediated relaxation after exposure to H-R --- p.53 / Chapter 3.5.2 --- EDHF-mediated relaxation after H-R in ST solution at different temperature --- p.54 / Chapter 3.5.3 --- Effect of addition of nicorandil to Krebs or ST solution during H-R on EDHF-mediated relaxation --- p.55 / Chapter 3.5.4 --- Clinical implications --- p.56 / Chapter Chapter 4. --- Hypoxia-Reoxygenation in Cardiac Microveins: Combined Effect with Cardioplegia and Temperature on the Endothelial Function --- p.68 / Chapter 4.1 --- Abstract --- p.68 / Chapter 4.2 --- Introduction --- p.69 / Chapter 4.3 --- Experimental design and analysis --- p.73 / Chapter 4.3.1 --- Vessel Preparation --- p.73 / Chapter 4.3.2 --- Normalization --- p.73 / Chapter 4.3.3 --- Hypoxia --- p.73 / Chapter 4.3.4 --- Effect of H-R on EDHF-mediated relaxation in cardiac micro veins --- p.74 / Chapter 4.3.5 --- Combined effects of H-R and ST solution on EDHF-mediated relaxation in cardiac microveins --- p.74 / Chapter 4.3.6 --- Data analysis --- p.75 / Chapter 4.4 --- Results --- p.75 / Chapter 4.4.1 --- Resting force --- p.75 / Chapter 4.4.2 --- U46619-induced contraction force --- p.76 / Chapter 4.4.3 --- Partial pressure of oxygen in hypoxia --- p.76 / Chapter 4.4.4 --- EDHF-mediated relaxation after H-R in Krebs solution at 37°C --- p.76 / Chapter 4.4.5 --- EDHF-mediated relaxation after exposure to H-R in ST solution at different temperatures --- p.77 / Chapter 4.5 --- Discussion --- p.78 / Chapter 4.5.1 --- Effect of H-R on EDHF-mediated relaxation --- p.78 / Chapter 4.5.2 --- Combined effects of H-R with ST solution on EDHF-mediated relaxation --- p.80 / Chapter 4.5.3 --- Clinical implications / Chapter Chapter 5. --- General Discussion --- p.89 / Chapter 5.1 --- EDHF-mediated endothelial function in porcine coronary circulation --- p.89 / Chapter 5.1.1 --- EDHF in porcine coronary microarteries --- p.92 / Chapter 5.1.2 --- EDHF in porcine cardiac veins --- p.90 / Chapter 5.2 --- Alteration of EDHF-mediated function after exposure to H-R --- p.91 / Chapter 5.2.1 --- In coronary microarteries --- p.91 / Chapter 5.2.2 --- In cardiac veins --- p.92 / Chapter 5.3 --- Alteration of EDHF-mediated function after exposure to ST solution under H-R --- p.92 / Chapter 5.3.1 --- In coronary microarteries --- p.93 / Chapter 5.3.2 --- In cardiac veins --- p.93 / Chapter 5.4 --- EDHF-mediated function in nicorandil-supplemented ST solution under H-R in coronary microarteries --- p.93 / Chapter 5.5 --- Clinical implications / Chapter 5.5.1 --- H-R injury --- p.94 / Chapter 5.5.2 --- H-R injury and cardioplegic solution --- p.95 / Chapter 5.5.2 --- Nicorandil-supplementation in cardioplegic solution --- p.95 / Chapter 5.6 --- Limitation of the study --- p.96 / Chapter 5.7 --- Future investigations --- p.96 / Chapter 5.8 --- Conclusions --- p.97 / References --- p.99

Ho, Kwok Wa. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2007. / Includes bibliographical references (leaves 60-65). / Abstracts in English and Chinese. / Chapter Chapter I / Chapter 1.1. --- Thromboxane A2 (TP) Receptors --- p.1 / Chapter 1.1.1. --- Gene structure of human TP receptors --- p.1 / Chapter 1.1.2. --- Isoforms of TP receptor --- p.1 / Chapter 1.1.3. --- Distribution and expression of TP receptors in human --- p.2 / Chapter 1.1.4. --- Signal transduction of TP receptors --- p.4 / Chapter 1.1.5. --- Major agonists of TP receptor in animals and humans --- p.7 / Chapter 1.1.5.1. --- Thromboxane A2 --- p.7 / Chapter 1.1.5.2. --- Prostaglandin H2 --- p.7 / Chapter 1.1.6. --- Functional studies: effect of TP receptor activation and blockade on vascular tone and atherosclerosis --- p.8 / Chapter 1.1.6.1. --- Effect of TP receptor activation --- p.8 / Chapter 1.1.6.1.1. --- On vaso-contraction --- p.8 / Chapter 1.1.6.1.2. --- On vaso-relaxation --- p.9 / Chapter 1.1.6.2. --- Effect of TP receptor blockade --- p.9 / Chapter 1.1.6.2.1. --- On endothelium dependent vaso-contraction --- p.9 / Chapter 1.1.6.2.2. --- On animal models related to atherosclerosis --- p.10 / Chapter 1.1.7. --- Objectives of current study --- p.10 / Chapter 1.2. --- Periadventitial Adipose (Fat) Tissue --- p.12 / Chapter 1.2.1. --- "General function, distribution and classification of fat" --- p.12 / Chapter 1.2.2. --- Representative endocrine/paracrine role of adipose tissues --- p.13 / Chapter 1.2.2.1. --- Leptin --- p.13 / Chapter 1.2.2.2. --- Angiotensinogen --- p.14 / Chapter 1.2.3. --- Functional studies on vessels with periadventital fat attached -The beginning of the story of adipcyte-derived relaxing factor (ADRF) --- p.15 / Chapter 1.2.3. --- Mechanisms behind the action of ADRF --- p.17 / Chapter 1.2.3.1. --- Nature of ADRF --- p.17 / Chapter 1.2.3.2. --- The mechanisms controlling the release of ADRF --- p.17 / Chapter 1.2.3.3. --- Proposed mechanisms explaining the anti-contractile effect mediated by ADRF --- p.17 / Chapter 1.2.4. --- Objectives of current study --- p.20 / Chapter Chapter II / Chapter 2.1. --- Tissue Preparation --- p.21 / Chapter 2.1.1. --- Preparation of blood vessels --- p.21 / Chapter 2.1.2. --- Procedures to remove the endothelium --- p.21 / Chapter 2.2. --- The Organ Bath Setups --- p.22 / Chapter 2.3. --- Calculation of Results --- p.24 / Chapter 2.3.1. --- Calculation of active tension --- p.24 / Chapter 2.3.2. --- Measurement of dry weight of arterial rings --- p.24 / Chapter 2.3.3. --- Measurement of the weight for periadventitial fat --- p.24 / Chapter 2.3.4. --- Statistic analysis --- p.24 / Chapter 2.4. --- Chemicals and Solutions --- p.25 / Chapter 2.4.1. --- Chemicals --- p.25 / Chapter 2.4.2. --- Solutions --- p.26 / Chapter Chapter III --- Stimulation of TP receptors by U46619 inhibits cGMP dependent vaso-relaxation --- p.27 / Chapter 3.1. --- Detail methods and materials --- p.27 / Chapter 3.1.1. --- "Safety announcement, tissue preparation and materials" --- p.27 / Chapter 3.1.1. --- Protocol --- p.27 / Chapter 3.1.1.1. --- PartI --- p.27 / Chapter 3.1.1.2. --- Part II --- p.28 / Chapter 3.1.1.3. --- Part III --- p.28 / Chapter 3.2. --- Results --- p.29 / Chapter 3.2.1. --- Effect of U46619 on vaso-relaxation --- p.29 / Chapter 3.2.2. --- Effect of Rho kinase and phosphodiesterase inhibitor on the inhibitory effect of U46619 --- p.29 / Chapter 3.2.3. --- The effect of low concentration of U46619 on vaso-relaxation --- p.29 / Chapter 3.3. --- Discussion --- p.37 / Chapter 3.3.1. --- Implication of the current study --- p.37 / Chapter 3.3.2. --- Formulated Theory --- p.41 / Chapter Chapter IV --- Effect of periadventitial fat on anti-relaxation effect induced by U46619 - A preliminary test --- p.43 / Chapter 4.1. --- Detail methods and materials --- p.43 / Chapter 4.1.1. --- "Safety announcement, tissue preparation and materials" --- p.43 / Chapter 4.1.2. --- Protocol --- p.43 / Chapter 4.1.2.1. --- Part I --- p.43 / Chapter 4.1.2.2. --- Part II --- p.44 / Chapter 4.1.2.3. --- Part III --- p.44 / Chapter 4.1.2.4. --- Part IV --- p.44 / Chapter 4.2. --- Results --- p.45 / Chapter 4.2.1. --- Effect of periadventitial fat on vaso-relaxation of rings contracted by phenylephrine --- p.45 / Chapter 4.2.2. --- Effect of periadventitial fat on vaso-relaxation of rings contracted by U46619 plus phenylephrine --- p.45 / Chapter 4.2.3. --- Effect of S18886 on vaso-relaxation in endothelium removed rings --- p.45 / Chapter 4.2.4. --- Effect of elevated extracellular potassium ions on vaso-relaxation --- p.46 / Chapter 4.3. --- Discussion --- p.56 / Chapter 4.3.1. --- Implication of current study --- p.56 / Chapter 4.3.2. --- Improvements and future perspectives of current study --- p.58 / Summary --- p.59 / References --- p.60

A disfunção endotelial atua tanto na aterogênese como na precipitação das síndromes coronárias agudas. A redução da biodisponibilidadedo óxido nítrico é expressão de endotélio disfuncional. O mecanismo desta redução não está elucidado. A presença de disfunção endotelialfoi correlacionada com fatores de risco (FR), nitrato sanguíneo e fatores genéticos (polimorfismo da óxido nítrico sintase endotelial, fibrinogênio e PAI-1) em um grupo de 128 pacientes com infarto do miocárdio (IAM) e idade = 40 anos, submetidos a ultra-som de artéria braquial. Os resultados foram comparados com um grupo jovens saudáveis. Verificou-se que pacientes jovens com IAM apresentavam disfunção endotelial em associação com FR, alterações bioquímicas e níveis aumentados de nitrato, porém sem alterações genéticas / The endothelial dysfunction plays an important roll in the atherogenesis and precipitation of acute coronary syndromes. The reduction of bioavailability of the nitric oxide is the expression of endothelial dysfunction. The exact mechanism of this reduction is not yet well explained. In order to evaluate the presence of endothelial dysfunction and correlation with risk factors (FR), nitrate blood levels and genetic factors (endothelial nitric oxide synthease polymorphism, fibrinogen and PAI-1) a 128 myocardial infarction patients group with age = 40 year was studied, and underwent a brachial artery ultra-sound. The results were compared with a group of young health individuals. The study found that the young patients with myocardial infarctions showed endothelial dysfunction with associated risks factors, biochemical changes and higher levels of nitrate, although without any significant genetic changes