Ng Chau Wah Stephen. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2003. / Includes bibliographical references (leaves 120-135). / Abstracts in English and Chinese. / Abstract --- p.i / Acknowledgements --- p.viii / Publications --- p.ix / Abbreviations --- p.x / Chapter Chapter 1 --- Introduction / Chapter 1.1 --- Traditional Chinese Medicine --- p.1 / Chapter 1.2 --- Danshen --- p.7 / Chapter 1.2.1 --- Chemical constituents of Danshen --- p.7 / Chapter 1.2.2 --- Pharmacology of Danshen --- p.10 / Chapter 1.3 --- Vascular system --- p.13 / Chapter 1.3.1 --- Physiology of blood vessels --- p.13 / Chapter 1.3.2 --- Vascular smooth muscle contraction --- p.14 / Chapter 1.3.3 --- Mechanism of vascular smooth muscle contraction --- p.15 / Chapter 1.3.3.1 --- Adrenoceptor in vascular system --- p.19 / Chapter 1.3.3.2 --- Muscarinic receptor in vascular system --- p.20 / Chapter 1.3.3.3 --- Synthesis and release of Nitric Oxide (NO)in vascular system --- p.22 / Chapter 1.3.3.4 --- Synthesis and release of postanoidsin vascular system --- p.25 / Chapter 1.3.3.5 --- Synthesis and release of histaminein vascular system --- p.28 / Chapter 1.3.3.6 --- Synthesis and release of Calcitonin gene-related peptide in vascular system --- p.29 / Chapter 1.4 --- Aims of the studies --- p.33 / Chapter Chapter 2 --- Materials and methods / Chapter 2.1 --- Materials --- p.35 / Chapter 2.2 --- Methods - General procedures --- p.35 / Chapter 2.2.1 --- Preparations of drug solutions --- p.35 / Chapter 2.2.2 --- Animals used and anaesthetization --- p.36 / Chapter 2.2.3 --- Cannulation of carotid artery and jugular vein --- p.37 / Chapter 2.2.4 --- Blood pressure measurement --- p.37 / Chapter 2.2.5 --- Knee joint denervation --- p.38 / Chapter 2.2.6 --- Knee joint blood flow measurement --- p.39 / Chapter 2.3 --- Methods - Specific procedures --- p.41 / Chapter 2.3.1 --- Validation of Laser Doppler Imaging (LDI) measurements --- p.41 / Chapter 2.3.2 --- Actions of topical administration of Danshen --- p.42 / Chapter 2.3.2.1 --- Studies of the mechanism(s) of action of Danshen --- p.43 / Chapter 2.3.2.2 --- Investigation for α-adrenoceptor antagonist activity --- p.44 / Chapter 2.3.2.3 --- Investigation for neural involvement --- p.44 / Chapter 2.3.3 --- Actions of intravenous administration of Danshen --- p.45 / Chapter 2.3.4 --- Data analysis --- p.45 / Chapter Chapter 3 --- Results / Chapter 3.1 --- Validation of LDI measurement --- p.47 / Chapter 3.2 --- Actions of intravenous administration of Danshen --- p.53 / Chapter 3.3 --- Actions of topical administration of Danshen --- p.53 / Chapter 3.4 --- Muscarinic receptor antagonist on Danshen --- p.61 / Chapter 3.5 --- β-adrenoceptor antagonist on Danshen --- p.67 / Chapter 3.6 --- Danshen on α-adrenoceptor agonist-induced vasoconstriction --- p.74 / Chapter 3.7 --- Nitric oxide synthase inhibitor on Danshen --- p.79 / Chapter 3.8 --- Cyclo-oxygenase (COX) inhibitor on Danshen --- p.83 / Chapter 3.9 --- Histamine receptor antagonists on Danshen --- p.87 / Chapter 3.10 --- CGRP receptor antagonist on Danshen --- p.92 / Chapter 3.11 --- Effect of denervation on Danshen --- p.92 / Chapter Chapter 4 --- Discussion --- p.100 / Reference --- p.120

Chan Yau Chi. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2005. / Includes bibliographical references (leaves 157-177). / Abstracts in English and Chinese. / Contents / Declaration --- p.i / Acknowledgement --- p.ii / Abbreviations --- p.iii-iv / Abstract in English --- p.v-viii / Abstract in Chinese --- p.ix-xi / Contents --- p.xii-xvi / Chapter CHAPTER I - --- Introduction / Chapter 1.1. --- Selective Estrogen Receptor Modulators (SERMs) --- p.1 / Chapter 1.1.1. --- Raloxifene --- p.6 / Chapter 1.2. --- Mechanisms of Action of SERMs in Vascular System --- p.7 / Chapter 1.2.1. --- Estrogen --- p.7 / Chapter 1.2.2. --- Estrogen Receptors (ERs) --- p.8 / Chapter 1.2.3. --- General Mechanisms of Action of SERMs --- p.13 / Chapter 1.2.4. --- Actions of Raloxifene --- p.14 / Chapter 1.3. --- Effects of SERMs in Cardiovascular System --- p.14 / Chapter 1.3.1. --- Effects of SERMs on Endothelial Function --- p.15 / Chapter 1.3.2. --- Effects of SERMs on Vascular Smooth Muscle --- p.17 / Chapter 1.4. --- Effects of Raloxifene on Vascular Circulations --- p.18 / Chapter 1.4.1. --- Effects of Raloxifene on Systemic Circulation --- p.18 / Chapter 1.4.1.1. --- Preclinical Data --- p.18 / Chapter 1.4.1.1.1. --- Effects on Serum Lipids --- p.18 / Chapter 1.4.1.1.2. --- Effects on Inflammation Markers and Blood Coagulation --- p.19 / Chapter 1.4.1.1.3. --- Antioxidative Effects --- p.19 / Chapter 1.4.1.1.4. --- Effects on Nitric Oxide and Endothelial Function --- p.19 / Chapter 1.4.1.1.5. --- Effects on Vascular Smooth Muscle --- p.20 / Chapter 1.4.1.1.6. --- "Vascular Injury, Atherosclerosis and Ischaemia-Reperfusion Injury" --- p.20 / Chapter 1.4.1.2. --- Clinical Studies - Effects in Post-Menopausal Women --- p.21 / Chapter 1.4.1.2.1. --- "Effects on Serum Lipids, Lipoproteins and Triglycerides" --- p.21 / Chapter 1.4.1.2.2. --- Effects on Inflammation Markers and Homocysteine --- p.22 / Chapter 1.4.1.2.3. --- Effects on Coagulation Markers --- p.23 / Chapter 1.4.1.2.4. --- Effects on Endothelial Function --- p.23 / Chapter 1.4.1.2.5. --- Cardiovascular Events --- p.23 / Chapter 1.5. --- Myogenic Response and Vascular System --- p.24 / Chapter 1.5.1. --- Initiation and Development of Myogenic Response --- p.25 / Chapter 1.5.2. --- Regulation of Myogenic Response --- p.26 / Chapter 1.5.2.1. --- 20-hydroxyeicosatetraenoic acid (20-HETE) --- p.26 / Chapter 1.5.2.2. --- "Protein Kinase C, Rho/Rho-Kinase, and Tyrosine Kinase" --- p.27 / Chapter 1.5.3. --- Myogenic Response and Endothelium --- p.31 / Chapter 1.5.4. --- Estrogen and Myogenic Tone --- p.31 / Chapter 1.6. --- Objectives of the Present Study --- p.32 / Chapter CHAPTER II - --- Methods and Materials / Chapter 2.1. --- Tissue and Cell Preparation --- p.34 / Chapter 2.1.1. --- Vessel Preparation --- p.34 / Chapter 2.1.2. --- Removal of a Functional Endothelium --- p.36 / Chapter 2.2. --- Myograph and Pressure Myograph Setups --- p.36 / Chapter 2.2.1. --- Myograph 一 Isometric Tension Measurement --- p.36 / Chapter 2.2.2. --- Pressure Myograph - Isobaric Diameter Measurement --- p.37 / Chapter 2.3. --- Intracellular [Ca2+] Measurement in Vascular Smooth Muscle --- p.42 / Chapter 2.4. --- Chronic Raloxifene Therapyin Spontaneously Hypertensive Rats (SHRs) and Wistar-Kyoto Rats (WKYs) --- p.42 / Chapter 2.4.1. --- Surgical Procedure - Raloxifene Tubing Insertion --- p.42 / Chapter 2.4.2. --- "Body Weight, Mean Arterial Blood Pressure and Uterine Weight" --- p.42 / Chapter 2.4.3. --- Measurement of Raloxifene Tubing Consumption --- p.43 / Chapter 2.4.4. --- Effect of Chronic Raloxifene Treatment on Artery Reactivity --- p.43 / Chapter 2.5. --- Ovariectomy and Chronic Raloxifene Therapyin Syrian Golden Hamsters --- p.45 / Chapter 2.5.1. --- Surgical Procedure - Ovariectomy (OVX) --- p.45 / Chapter 2.5.2. --- Surgical Procedure - Raloxifene Tubing Insertion --- p.45 / Chapter 2.5.3. --- High-Cholesterol Food Preparation --- p.45 / Chapter 2.5.4. --- "Body Weight, Food Consumption and Uterine Weight" --- p.46 / Chapter 2.5.5. --- Measurement of Raloxifene Tubing Consumption --- p.46 / Chapter 2.5.6. --- Serum Lipid and Lipoprotein Determinations --- p.46 / Chapter 2.5.7. --- Effect of Chronic Raloxifene on Artery Reactivity --- p.46 / Chapter 2.6. --- Solutions and Drugs --- p.49 / Chapter 2.6.1. --- "Drugs, Chemicals and Enzymes" --- p.49 / Chapter 2.6.2. --- Solutions --- p.51 / Chapter 2.6.3. --- Diet Composition for Syrian Golden Hamsters --- p.51 / Chapter 2.7. --- Statistical Analysis --- p.52 / Chapter CHAPTER III - --- "Raloxifene Relaxes Rat Pulmonary Arteries and Veins: Roles of Gender, Endothelium, and Antagonism of Ca Influx" / Chapter 3.1. --- Abstract --- p.53 / Chapter 3.2. --- Introduction --- p.54 / Chapter 3.3. --- Methods and Materials --- p.55 / Chapter 3.3.1. --- Blood Vessel Preparation --- p.55 / Chapter 3.3.2. --- Protocols --- p.55 / Chapter 3.3.3. --- Measurement of Vascular Smooth Muscle [Ca2+]i --- p.56 / Chapter 3.3.4. --- Drugs --- p.57 / Chapter 3.3.5. --- Data Analysis --- p.53 / Chapter 3.4. --- Results --- p.58 / Chapter 3.4.1. --- Effects of Raloxifene on Pulmonary Arteries --- p.53 / Chapter 3.4.2. --- Effect of Raloxifene on CaCl2-induced Constrictionin Pulmonary Arteries --- p.59 / Chapter 3.4.3. --- Effects of Raloxifene on Pulmonary Veins --- p.59 / Chapter 3.4.4. --- Effect of Raloxifene on CaCl2-stimulated Increases in [Ca2+]i in Pulmonary Arteries --- p.60 / Chapter 3.5. --- Discussion --- p.67 / Chapter 3.6. --- Conclusion --- p.69 / Chapter CHAPTER IV - --- Raloxifene Modulates Pulmonary Vascular Reactivity in Spontaneously Hypertensive Rats / Chapter 4.1. --- Abstract --- p.70 / Chapter 4.2. --- Introduction --- p.71 / Chapter 4.3. --- Methods and Materials --- p.72 / Chapter 4.3.1. --- Raloxifene Treatment --- p.72 / Chapter 4.3.2. --- Blood Vessel Preparation --- p.72 / Chapter 4.3.3. --- Protocols --- p.73 / Chapter 4.3.4. --- Chemicals and Drugs --- p.73 / Chapter 4.3.5. --- Data Analysis --- p.74 / Chapter 4.4. --- Results --- p.74 / Chapter 4.4.1. --- Blood Pressure --- p.74 / Chapter 4.4.2. --- Vasocontraction in Spontaneously Hypertensive Rats --- p.75 / Chapter 4.4.3. --- Vasorelaxation in Spontaneously Hypertensive Rats --- p.75 / Chapter 4.4.4. --- Vasocontraction in Wistar-Kyoto rats --- p.76 / Chapter 4.4.5. --- Vasorelaxation in Wistar-Kyoto rats --- p.77 / Chapter 4.4.6. --- Comparison of contraction between WKY and SHR rats --- p.78 / Chapter 4.4.7. --- Comparison of relaxation between WKY and SHR rats --- p.78 / Chapter 4.5. --- Discussion --- p.93 / Chapter 4.6. --- Conclusion --- p.96 / Chapter CHAPTER V - --- Effects of Therapeutic Concentrations of Raloxifene in Pressurized Rat Small Mesenteric Artery / Chapter 5.1. --- Abstract --- p.98 / Chapter 5.2. --- Introduction --- p.99 / Chapter 5.3. --- Methods and Materials --- p.101 / Chapter 5.3.1. --- Blood Vessel Preparation --- p.101 / Chapter 5.3.2. --- Experimental Protocols --- p.102 / Chapter 5.3.2.1. --- Myogenic Tone Development --- p.102 / Chapter 5.3.2.2. --- Effects of Raloxifene and 17β-EstradioI on Myogenic Constriction --- p.102 / Chapter 5.3.2.3. --- Effects of Pharmacological Inhibitors on Raloxifene- or 17β-Estradiol-induced Myogenic Constriction --- p.103 / Chapter 5.3.3. --- Drugs and Solutions --- p.103 / Chapter 5.3.4. --- Expression of Results and Statistical Analysis --- p.104 / Chapter 5.4. --- Results --- p.104 / Chapter 5.4.1. --- Effects of Raloxifene and 17β-Estradiol on Rat Resistance Mesenteric Arteries1 --- p.104 / Chapter 5.4.2. --- Effects of Inhibitors of NOS --- p.105 / Chapter 5.4.3. --- Effect of CTX plus Apamin --- p.106 / Chapter 5.4.4. --- "Effect of ICI 182,780" --- p.106 / Chapter 5.4.5. --- "Effects of Wortmannin, LY 294002 and Cycloheximide" --- p.106 / Chapter 5.5. --- Discussion --- p.122 / Chapter 5.6. --- Conclusion --- p.125 / Chapter CHAPTER VI - --- Effects of Chronic Raloxifene Treatment on Vascular Reactivity in Pressurized Septal Coronary Arteries from Hamsters Fed with High-Cholesterol Diet / Chapter 6.1. --- Abstract --- p.127 / Chapter 6.2. --- Introduction --- p.128 / Chapter 6.3. --- Methods and Materials --- p.129 / Chapter 6.3.1. --- Preparatory Work --- p.129 / Chapter 6.3.1.1. --- Animals and Diets --- p.129 / Chapter 6.3.1.2. --- Preparation of High-Cholesterol (HC) Food --- p.129 / Chapter 6.3.1.3. --- Surgical Procedure - Ovariectomy (OVX) --- p.129 / Chapter 6.3.1.4. --- Surgical Procedure - Raloxifene Tubing Insertion --- p.130 / Chapter 6.3.1.5. --- Blood Vessel Preparation --- p.130 / Chapter 6.3.1.6. --- "Body Weight, Food Consumption and Uterine Weight" --- p.131 / Chapter 6.3.1.7. --- Measurement of Raloxifene Tubing Consumption --- p.131 / Chapter 6.3.1.8. --- Serum Lipid and Lipoprotein Determinations --- p.132 / Chapter 6.3.2. --- Experimental Protocols --- p.132 / Chapter 6.3.2.1. --- Development of Myogenic Tone --- p.132 / Chapter 6.3.2.2. --- Pressure-Diameter Relationships --- p.132 / Chapter 6.3.2.3. --- The Effect of Acetylcholine --- p.133 / Chapter 6.3.2.4. --- The Effect of U46619 --- p.133 / Chapter 6.3.2.5. --- The Effect of L-NAME --- p.133 / Chapter 6.3.3. --- Drugs and Solutions --- p.133 / Chapter 6.3.4. --- Expression of Results and Statistical Analysis --- p.134 / Chapter 6.4. --- Results --- p.135 / Chapter 6.4.1. --- Effects on Myogenic Response --- p.135 / Chapter 6.4.2. --- "Effects of Acetylcholine, U46619 and L-NAME" --- p.135 / Chapter 6.4.2.1. --- Comparison between OHHCD and OvxOHHCD --- p.135 / Chapter 6.4.2.2. --- Comparison between OvxOHHCD and OvxOHHCDRf --- p.135 / Chapter 6.4.2.3. --- Comparison between OHHCDRf and OvxOHHCDRf --- p.136 / Chapter 6.4.2.4. --- Comparison between OHHCD and OHHCDRf --- p.136 / Chapter 6.5. --- Discussion --- p.155 / Chapter 6.6. --- Conclusion --- p.156 / References --- p.157 / Publications --- p.176

Cheung Ho Yan. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2005. / Includes bibliographical references (leaves 164-175). / Abstracts in English and Chinese. / Abstract --- p.i / Acknowledgements --- p.vi / Publications based on the work in this thesis --- p.vii / Table of content --- p.viii / Abbreviations --- p.xii / Chapter CHAPTER 1 --- INTRODUCTION --- p.1 / Chapter 1.1 --- Traditional Chinese Medicine --- p.1 / Chapter 1.1.1 --- Danshen --- p.2 / Chapter 1.1.2 --- Chemical constituents --- p.5 / Chapter 1.1.3 --- Pharmacological effects --- p.7 / Chapter 1.1.3.1 --- On blood vessels --- p.7 / Chapter 1.1.3.2 --- On blood pressure --- p.8 / Chapter 1.1.3.3 --- On heart --- p.8 / Chapter 1.1.3.4 --- On myocardial ischaemia and reperfusion --- p.9 / Chapter 1.1.3.5 --- On platelet activity --- p.10 / Chapter 1.1.3.6 --- Other actions --- p.11 / Chapter 1.1.4 --- Clinical studies --- p.12 / Chapter 1.2 --- The Vascular System --- p.13 / Chapter 1.2.1 --- The circulation network --- p.13 / Chapter 1.2.2 --- Physiology of blood vessels --- p.13 / Chapter 1.2.3 --- Control of vascular lone --- p.14 / Chapter 1.3 --- Mechanisms of Vasodilatation --- p.16 / Chapter 1.3.1 --- Endothelium derived relaxant factors (EDRFs) --- p.16 / Chapter 1.3.1.1 --- Nitric oxide (NO) --- p.16 / Chapter 1.3.1.2 --- Prostacyclin (PGI：) --- p.17 / Chapter 1.3.1.3 --- Endotheliun-derived hyperpolarization factors (EDHFs) --- p.18 / Chapter 1.3.1.3.1 --- Epoxyeicosatrienoic acids (EETs) --- p.19 / Chapter 1.3.1.3.2 --- Potassium ion (IC) --- p.20 / Chapter 1.3.1.3.3 --- Gap junction --- p.20 / Chapter 1.3.2 --- Signal transduction pathways --- p.21 / Chapter 1.3.2.1 --- Guanylyl cyclase-cGMP pathway --- p.21 / Chapter 1.3.2.2 --- Adenylyl cyclase-cAMP pathway --- p.22 / Chapter 1.3.3 --- Ion channels in vascular smooth muscle cell --- p.24 / Chapter 1.3.3.1 --- Potassium channels (K+ channels) --- p.24 / Chapter 1.3.3.2 --- Calcium channels (Ca2+ channels) --- p.24 / Chapter 1.3.3.3 --- Chloride channel (Cl channel) --- p.25 / Chapter 1.3.4 --- Receptor-operated mechanisms --- p.27 / Chapter 1.3.4.1 --- Muscarinic receptors --- p.27 / Chapter 1.3.4.2 --- Adrenoceptors --- p.27 / Chapter 1.3.4.3 --- Histamine receptors --- p.28 / Chapter 1.3.4.4 --- CGRP receptors --- p.29 / Chapter 1.3.4.5 --- Tachykinin receptors --- p.30 / Chapter 1.4 --- Aims of the studies --- p.31 / Chapter CHAPTER 2 --- MATERIALS AND METHODS --- p.32 / Chapter 2.1 --- Extraction of Water and Lipid-solubie Fractions from Danshen --- p.32 / Chapter 2.1.1 --- Preparation of water-soluble and lipid-soluble fractions --- p.33 / Chapter 2.2 --- Experiments on Rat Knee Joint --- p.35 / Chapter 2.2.1 --- Animals --- p.35 / Chapter 2.2.2 --- Materials --- p.35 / Chapter 2.2.3 --- Preparatory protocols --- p.37 / Chapter 2.2.3.1 --- Anaesthesia of animals --- p.37 / Chapter 2.2.3.2 --- Cannulation of trachea --- p.37 / Chapter 2.2.3.3 --- Cannulation of carotid artery --- p.38 / Chapter 2.2.3.4 --- Blood pressure measurement --- p.38 / Chapter 2.2.4 --- Measurement of knee joint blood flow --- p.39 / Chapter 2.2.4.1 --- Preparation for measurement of knee joint blood flow --- p.41 / Chapter 2.2.5 --- Experimental protocols --- p.41 / Chapter 2.2.5.1 --- Danshen on knee joint blood flow --- p.41 / Chapter 2.2.5.2 --- Antagonists on Danshen --- p.41 / Chapter 2.2.5.3 --- Positive controls --- p.43 / Chapter 2.2.6 --- Image analysis --- p.44 / Chapter 2.2.7 --- Data analysis --- p.44 / Chapter 2.3 --- Experiments on Rat Femoral Artery --- p.45 / Chapter 2.3.1 --- Animals --- p.45 / Chapter 2.3.2 --- Materials --- p.45 / Chapter 2.3.2.1 --- Chemicals --- p.45 / Chapter 2.3.2.2 --- Physiological salt solution --- p.48 / Chapter 2.3.3 --- Preparatory protocols --- p.48 / Chapter 2.3.3.1 --- Small vessel myograph --- p.48 / Chapter 2.3.3.2 --- Isolation and mounting of tissue --- p.49 / Chapter 2.3.4 --- Experimental protocols --- p.50 / Chapter 2.3.4.1 --- Studies on the vasodilator response to Danshen --- p.50 / Chapter 2.3.4.2 --- Studies of antagonists on Danshen --- p.50 / Chapter 2.3.4.2.1 --- Endothelium-dependent mechanisms --- p.51 / Chapter 2.3.4.2.2 --- Endothelium-independent mechanisms --- p.54 / Chapter 2.3.4.2.3 --- K+ channel blockers --- p.54 / Chapter 2.3.4.2.4 --- Positive controls --- p.55 / Chapter 2.3.4.3 --- Danshen on Ca2+-induced contraction --- p.56 / Chapter 2.3.5 --- Data analysis --- p.57 / Chapter CHAPTER 3 --- RESULTS --- p.58 / Chapter 3.1 --- Danshen on Rat Knee Joint Blood Flow --- p.58 / Chapter 3.1.1 --- Topical administration of Danshen --- p.58 / Chapter 3.1.2 --- Antagonists on Danshen --- p.59 / Chapter 3.1.2.1 --- Muscarinic receptor antagonist --- p.59 / Chapter 3.1.2.2 --- β-adrenoceptor antagonist --- p.60 / Chapter 3.1.2.3 --- Histamine receptor antagonists --- p.60 / Chapter 3.1.2.4 --- Nitric oxide synthase inhibitor --- p.61 / Chapter 3.1.2.5 --- Cyclo-oxygenase inhibitors --- p.62 / Chapter 3.1.2.6 --- CGRPi receptor antagonist --- p.62 / Chapter 3.1.2.7 --- NK1 receptor antagonist --- p.63 / Chapter 3.1.2.8 --- Potassium channel inhibitor --- p.64 / Chapter 3.1.2.9 --- "Combination of cyclo-oxygenase inhibitor, nitric oxide synthase inhibitor and CGRP1 receptor antagonist" --- p.64 / Chapter 3.1.3 --- Antagonists on water-soluble fraction of Danshen --- p.91 / Chapter 3.1.3.1 --- Nitric oxide synthase inhibitor --- p.91 / Chapter 3.1.3.2 --- Cyclo-oxygenase inhibitors --- p.91 / Chapter 3.1.3.3 --- CGRP1 receptor antagonist --- p.92 / Chapter 3.1.3.4 --- NK1 receptor antagonist --- p.92 / Chapter 3.1.3.5 --- Potassium channel inhibitor --- p.92 / Chapter 3.2 --- Danshen on Rat Femoral Artery --- p.99 / Chapter 3.2.1 --- Danshen on precontracted arterial ring --- p.99 / Chapter 3.2.2 --- Endothelium-dependent mechanisms --- p.106 / Chapter 3.2.3 --- Endothelium-independent mechanisms --- p.114 / Chapter 3.2.4 --- K+ channel blockers --- p.119 / Chapter 3.2.4.1 --- Effect on Danshen --- p.119 / Chapter 3.2.4.2 --- Effect on water-soluble and lipid-soluble fractions of Danshen --- p.121 / Chapter 3.2.4.3 --- Effect on Danshensu --- p.122 / Chapter 3.2.5 --- Danshen on Ca2+-induced contractions --- p.133 / Chapter CHAPTER 4 --- DISCUSSION --- p.138 / Chapter 4.1 --- In Vivo Studies of Danshen on Rat Knee Joint Blood Flow --- p.139 / Chapter 4.2 --- In Vitro Studies of Danshen on Isolated Rat Femoral Artery --- p.148 / Chapter 4.2.1 --- Comparisons of the use of different precontractors --- p.148 / Chapter 4.2.2 --- Investigations on endothelium-dependent mechanisms --- p.151 / Chapter 4.2.3 --- Investigations on endothelium-independent mechanisms --- p.152 / Chapter 4.2.4 --- Effects of K+ channel blockers --- p.154 / Chapter 4.2.5 --- Inhibition of Ca2+ influx in vascular smooth muscle --- p.157 / Chapter 4.3 --- Comparisons of Results from In Vivo and In Vitro Studies --- p.159 / Chapter 4.4 --- Future Studies --- p.161 / Chapter 4.5 --- Conclusion --- p.162 / REFERENCES --- p.164

Ng Chi Ho. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2005. / Includes bibliographical references (leaves 147-160). / Abstracts in English and Chinese. / ACKNOWLEDGMENTS --- p.I / ABSTRACT --- p.II / LIST OF ABBREVIATIONS --- p.VII / TABLE OF CONTENTS --- p.IX / Chapter CHAPTER 1 --- GENERAL INTRODUCTION / Chapter 1.1 --- Introduction of Low-density lipoprotein --- p.1 / Chapter 1.1.1 --- What are lipids? --- p.1 / Chapter 1.1.2 --- Function and structure of cholesterol --- p.1 / Chapter 1.1.3 --- Function and classification of lipoprotein --- p.1 / Chapter 1.2 --- Functions of low-density lipoprotein --- p.2 / Chapter 1.3 --- Basic structure of low-density lipoprotein --- p.4 / Chapter 1.4 --- Principle on isolation and purification of low-density lipoprotein --- p.4 / Chapter 1.5 --- Cholesterol transport system --- p.7 / Chapter 1.5.1 --- Exogenous pathway of cholesterol metabolism --- p.7 / Chapter 1.5.2 --- Endogenous pathway of cholesterol metabolism --- p.7 / Chapter 1.5.3 --- Reverse transport of Cholesterol --- p.8 / Chapter 1.6 --- Oxidation of LDL --- p.10 / Chapter 1.6.1 --- Agents that causes oxidation --- p.10 / Chapter 1.6.1.1 --- Lipoxygenases --- p.10 / Chapter 1.6.1.2 --- Myeloperoxidase --- p.10 / Chapter 1.6.1.3 --- Reactive nitrogen species --- p.11 / Chapter 1.6.1.4 --- Reactive oxygen species --- p.11 / Chapter 1.6.2 --- Factors that affect the susceptibility of LDL oxidation --- p.13 / Chapter 1.7 --- Hyperlipidaemia 一 chance to increase LDL oxidation --- p.13 / Chapter 1.7.1 --- Definition of hyperlipidemia and hypercholesterolemia --- p.13 / Chapter 1.7.2 --- Risk factors of hyperlipidaemia --- p.13 / Chapter 1.7.2.1 --- High fat low fibre diets: --- p.13 / Chapter 1.7.2.2 --- Obesity --- p.14 / Chapter 1.7.2.3 --- Type II diabetes --- p.14 / Chapter 1.7.2.4 --- Genetic factors (Familial hyperlipidemias) --- p.14 / Chapter 1.8 --- Diseases related to oxidized LDL --- p.15 / Chapter 1.8.1 --- Cardiovascular diseases --- p.15 / Chapter 1.8.1.1 --- Atherosclerosis and ischemic heart attack --- p.15 / Chapter 1.8.1.2 --- Factors that affect incidence of atherosclerosis --- p.16 / Chapter 1.8.1.2.1 --- Triglyceride-rich lipoprotein --- p.16 / Chapter 1.8.1.2.2 --- Small and dense LDL --- p.16 / Chapter 1.8.1.3 --- Stroke --- p.17 / Chapter 1.8.2 --- Common ways to reduce plasma cholesterol level --- p.17 / Chapter 1.8.2.1 --- Diet control --- p.17 / Chapter 1.8.2.2 --- Physical activity --- p.17 / Chapter 1.8.2.3 --- Drug therapy --- p.18 / Chapter CHAPTER 2 --- IMPAIRMENT OF OXIDIZED LDL ON ENDOTHELIUM-DEPENDENT RELAXATION / Chapter 2.1 --- Introduction --- p.19 / Chapter 2.1.1 --- Properties and function of phenylephrine hydrochloride --- p.22 / Chapter 2.1.2 --- Properties and function of acetylcholine --- p.22 / Chapter 2.2 --- Objectives --- p.23 / Chapter 2.3 --- Materials and methods --- p.24 / Chapter 2.3.1 --- Preparation of drugs --- p.24 / Chapter 2.3.2 --- Preparation of human native LDL --- p.25 / Chapter 2.3.3 --- Preparation of oxidized LDL --- p.27 / Chapter 2.3.4 --- Preparation of aorta --- p.27 / Chapter 2.3.5 --- Measurement of Isometric Force in vitro --- p.30 / Chapter 2.3.5.1 --- Protocol 1- Dose effect of oxidized LDL on acetylcholine-induced vasorelaxation --- p.30 / Chapter 2.3.5.2 --- Protocol 2 - Time effect of oxidized LDL on acetylcholine-induced vasorelaxation --- p.30 / Chapter 2.3.5.3 --- Protocol 3 - Effect of co-incubation of LDL and copper(ll) sulphate on acetylcholine-induced vasorelaxation --- p.31 / Chapter 2.3.5.4 --- Protocol 4 - Effect of oxidized LDL on selected vasodilators --- p.32 / Chapter 2.3.5.5 --- Protocol 5 - Effect of pretreatment of L-arginine on oxidized LDL impaired -endothelium-induced relaxation --- p.32 / Chapter 2.3.5.6 --- Protocol 6 - Effect of a -tocopherol on oxidized LDL-damaged acetylcholine- induced vasorelaxation --- p.33 / Chapter 2.3.5.7 --- Protocol 7 - Effect of a -tocopherol on LDL and copper(ll) sulphate- induced endothelial dysfunction --- p.33 / Chapter 2.3.6 --- Western blot analysis of endothelial nitric oxide synthase (eNOS) protein --- p.34 / Chapter 2.3.7 --- Statistics --- p.35 / Chapter 2.4 --- Results --- p.36 / Chapter 2.4.1 --- Dose effect of oxidized LDL on acetylcholine-induced vasorelaxation --- p.36 / Chapter 2.4.2 --- Time effect of oxidized LDL on acetylcholine-induced vasorelaxation --- p.36 / Chapter 2.4.3 --- Effect of co-incubation of LDL and copper(II) sulphate on acetylcholine- induced vasorelaxation --- p.39 / Chapter 2.4.4 --- Effect of oxidized LDL on selected vasodilators --- p.41 / Chapter 2.4.5 --- Effect of pretreatment of L-arginine on oxidized LDL impaired- acetylcholine-induced relaxation --- p.41 / Chapter 2.4.6 --- Effect of a-tocopherol on oxidized LDL-damaged acetylcholine- induced vasorelaxation --- p.48 / Chapter 2.4.7 --- Effect of a-tocopherol on LDL and copper(II) sulphate-induced endothelial dysfunction --- p.50 / Chapter 2.4.8 --- eNOS Protein expression --- p.50 / Chapter 2.5 --- Discussion --- p.53 / Chapter CHAPTER 3 --- EFFECTS OF LDL INJECTION ON THE ENDOTHELIAL FUNCTION OF RATS / Chapter 3.1 --- Introduction --- p.58 / Chapter 3.2 --- Objective --- p.60 / Chapter 3.3 --- Methods and Materials --- p.61 / Chapter 3.3.1 --- Preparation of Drugs --- p.61 / Chapter 3.3.2 --- Preparation of LDL --- p.61 / Chapter 3.3.3 --- Animal Treatment --- p.61 / Chapter 3.3.4 --- Serum lipid and lipoprotein determinations --- p.62 / Chapter 3.3.5 --- Measurement of serum MDA level by TBARS assay --- p.62 / Chapter 3.3.6 --- Preparation of aorta --- p.62 / Chapter 3.3.7 --- Organ bath experiment --- p.63 / Chapter 3.3.8 --- Statistics --- p.64 / Chapter 3.4 --- Result --- p.65 / Chapter 3.4.1 --- Growth and food intake --- p.65 / Chapter 3.4.2 --- "Effect of LDL injection on serum TC, TG and HDL-C" --- p.65 / Chapter 3.4.3 --- Effect of LDL injection on non-HDL-C and ratio of non-HDL-C to HDL-C --- p.65 / Chapter 3.4.4 --- Serum MDA level --- p.68 / Chapter 3.4.5 --- Phenylephrine-induced contraction --- p.70 / Chapter 3.4.6 --- Endothelium-dependent and -independent relaxation --- p.75 / Chapter 3.5 --- Discussion --- p.79 / Chapter CHAPTER 4 --- EFFECTS OF INDIVIDUAL COMPONENT OF OXIDIZED LDL ON ENDOTHELIUM-DEPENDENT RELAXATION / Chapter 4.1 --- Introduction --- p.83 / Chapter 4.2 --- Objectives --- p.85 / Chapter 4.3 --- Materials and methods --- p.86 / Chapter 4.3.1 --- Preparation of drugs --- p.86 / Chapter 4.3.2 --- Preparation of human native LDL and oxidized LDL --- p.86 / Chapter 4.3.3 --- GC analysis of fatty acid composition in LDL --- p.86 / Chapter 4.3.4 --- TBARS assay analysis of MDA content in LDL --- p.87 / Chapter 4.3.5 --- GC analysis of cholesterol oxidation products in LDL --- p.89 / Chapter 4.3.6 --- Thin-layer chromatography analysis of LPC in LDL --- p.91 / Chapter 4.3.7 --- Preparation of aorta --- p.92 / Chapter 4.3.8 --- Measurement of Isometric Force in vitro --- p.92 / Chapter 4.3.8.1 --- Protocol 1- effect of LPC on acetylcholine-induced vasorelaxation --- p.92 / Chapter 4.3.8.2 --- Protocol 2- effect of cholesterol oxidation products on acetylcholine-induced vasorelaxation --- p.92 / Chapter 4.3.8.3 --- Protocol 3- effect of oxidized fatty acids on acetylcholine-induced vasorelaxation --- p.93 / Chapter 4.3.9 --- Statistics --- p.93 / Chapter 4.4 --- Results --- p.94 / Chapter 4.4.1 --- Compositional differences between native LDL and oxidized LDL.… --- p.94 / Chapter 4.4.2 --- Effect of LPC on endothelium-dependent relaxation --- p.98 / Chapter 4.4.3 --- Effect of COPs on endothelium-dependent relaxation --- p.98 / Chapter 4.4.4 --- Effect of oxidized fatty acids on endothelium-dependent relaxation --- p.101 / Chapter 4.5 --- Discussion --- p.103 / Chapter CHAPTER 5 --- EFFECTS OF DIETARY OXIDIZED CHOLESTEROL ON BLOOD CHOLESTEROL LEVEL IN HAMSTERS / Chapter 5.1 --- Introduction --- p.107 / Chapter 5.2 --- Objectives --- p.111 / Chapter 5.3 --- Materials and Methods --- p.112 / Chapter 5.3.1 --- Preparation of Oxidized Cholesterol --- p.112 / Chapter 5.3.2 --- Diet preparation --- p.112 / Chapter 5.3.3 --- Animals --- p.113 / Chapter 5.3.4 --- Serum lipid and lipoprotein determinations --- p.116 / Chapter 5.3.5 --- GC analysis of cholesterol and cholesterol oxidation products on organs --- p.116 / Chapter 5.3.6 --- Extraction of neutral and acidic sterols from fecal samples --- p.117 / Chapter 5.3.6.1 --- Determination of neutral sterols --- p.117 / Chapter 5.3.6.2 --- Determination of acidic sterols --- p.117 / Chapter 5.3.6.3 --- GLC analysis of neutral and acidic sterols --- p.118 / Chapter 5.3.7 --- Organ bath experiment --- p.121 / Chapter 5.3.7.1 --- Preparation of aorta --- p.121 / Chapter 5.3.7.2 --- Aortic relaxation --- p.121 / Chapter 5.3.8 --- Analysis of the total area of atherosclerotic plaque on aorta --- p.122 / Chapter 5.3.9 --- Statistics --- p.122 / Chapter 5.4 --- Results --- p.123 / Chapter 5.4.1 --- GC of oxidized cholesterol --- p.123 / Chapter 5.4.2 --- Growth and food intake --- p.123 / Chapter 5.4.3 --- "Effect of non-oxidized and oxidized cholesterol on serum TC, TG and HDL-C" --- p.123 / Chapter 5.4.4 --- Effect of non-oxidized and oxidized cholesterol on non-HDL-C and ratio of non-HDL-C to HDL-C --- p.124 / Chapter 5.4.5 --- Effect ofnon-oxidized and oxidized cholesterol on concentration of hepatic cholesterol --- p.128 / Chapter 5.4.6 --- Effect of non-oxidized and oxidized cholesterol on concentration of cholesterol oxidation products accumulated in liver --- p.128 / Chapter 5.4.7 --- Effect of non-oxidized and oxidized cholesterol on concentration of brain and aortic cholesterol --- p.128 / Chapter 5.4.8 --- Effect of non-oxidized and oxidized cholesterol on fecal neutral and acidic sterols --- p.129 / Chapter 5.4.9 --- Effect of non-oxidized and oxidized cholesterol on aortic relaxation --- p.135 / Chapter 5.4.10 --- Effect of non-oxidzied and oxidized cholesterol on area of atherosclerotic plaque --- p.137 / Chapter 5.5 --- Discussion --- p.139 / Chapter CHAPTER 6 --- CONCLUSION --- p.143 / REFERENCES --- p.146