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Investigation of in vitro and in vivo effects of raloxifene on the pulmonary and systemic vascular circulations.

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

Identiferoai:union.ndltd.org:cuhk.edu.hk/oai:cuhk-dr:cuhk_325238
Date January 2005
ContributorsChan, Yau Chi., Chinese University of Hong Kong Graduate School. Division of Physiology.
Source SetsThe Chinese University of Hong Kong
LanguageEnglish, Chinese
Detected LanguageEnglish
TypeText, bibliography
Formatprint, xvi, 177 leaves : ill. ; 30 cm.
RightsUse of this resource is governed by the terms and conditions of the Creative Commons “Attribution-NonCommercial-NoDerivatives 4.0 International” License (http://creativecommons.org/licenses/by-nc-nd/4.0/)

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