Modulation of vascular reactivity by selective estrogen receptor modulators and dihydropyridines in porcine coronary arteries.

• Other Authors: Leung, Hok Sum.
• Format: Others
• Language: English; Chinese
• Published: 2005
• Subjects: Coronary circulation; Selective estrogen receptor modulators; Dihydropyridine; Coronary Circulation > drug effects; Selective Estrogen Receptor Modulators > therapeutic use; Selective Estrogen Receptor Modulators > metabolism; Dihydropyridines
• Online Access: http://library.cuhk.edu.hk/record=b5892728; http://repository.lib.cuhk.edu.hk/en/item/cuhk-325237

Leung Hok Sum. === Thesis (M.Phil.)--Chinese University of Hong Kong, 2005. === Includes bibliographical references (leaves 128-147). === Abstracts in English and Chinese. === Declaration --- p.i === Acknowledgements --- p.ii === Abbreviation --- p.iii === Abstract in English --- p.iv === Abstract in Chinese --- p.vi === Contents --- p.viii === Chapter Chapter I - --- Introduction === Chapter 1.1. --- Steroid Hormone --- p.1 === Chapter 1.2. --- Estrogen Receptors --- p.2 === Chapter 1.3. --- Selective Estrogen Receptor Modulators --- p.5 === Chapter 1.3.1. --- Tamoxifen --- p.5 === Chapter 1.3.1.1. --- Cardiovascular Effects of Tamoxifen --- p.6 === Chapter 1.3.1.2. --- Acute Vascular Effects of Tamoxifen --- p.6 === Chapter 1.3.1.3. --- Chronic Vascular Effects of Tamoxifen --- p.7 === Chapter 1.3.1.4. --- Antioxidant Effects of Tamoxifen --- p.8 === Chapter 1.3.2. --- Raloxifene --- p.8 === Chapter 1.3.2.1. --- Cardiovascular Effects of Raloxifene --- p.8 === Chapter 1.3.2.2. --- Acute Vascular Effects of Raloxifene --- p.9 === Chapter 1.3.2.3. --- Chronic Vascular Effects of Raloxifene --- p.10 === Chapter 1.3.2.4. --- Ovariectomy and Raloxifene Treatment --- p.11 === Chapter 1.4. --- Mechanism of Action of SERMs --- p.15 === Chapter 1.5. --- Effects of Functional Endothelium and Nitric Oxide --- p.18 === Chapter 1.6. --- Dihydropyridine (DHP) Calcium Channel Antagonists --- p.19 === Chapter 1.6.1. --- Development of Newer Generation of Dihydropyridines --- p.19 === Chapter 1.6.2. --- Effects of Dihydropyridines on Vascular Endothelium (I) --- p.20 === Chapter 1.6.3. --- Effects of Dihydropyridines on Vascular Endothelium (II) --- p.21 === Chapter 1.6.4. --- Effects of Dihydropyridines on Nitric Oxide Synthase (NOS) --- p.21 === Chapter 1.6.5. --- Clinical Studies of Dihydropyridines --- p.22 === Chapter 1.7. --- Vascular Ion Channels --- p.25 === Chapter 1.8. --- Objectives of The Present Study --- p.26 === Chapter Chapter II - --- Materials and Methods === Chapter 2.1. --- Tissue Preparation --- p.27 === Chapter 2.1.1. --- Preparation of The Porcine Left Circumflex Coronary Arteries --- p.27 === Chapter 2.1.2. --- Removal of Functional Endothelium --- p.27 === Chapter 2.1.3. --- Organ Bath Setup --- p.27 === Chapter 2.1.4. --- Isometric Force Measurement --- p.29 === Chapter 2.2. --- In situ Endothelial [Ca2+]i Imaging --- p.29 === Chapter 2.2.1. --- Preparation of Porcine Left Circumflex Coronary Arteries --- p.29 === Chapter 2.2.2. --- Setup For In situ Endothelial [Ca2+]i Imaging --- p.30 === Chapter 2.3. --- Electrophysiological Measurement of BKCa Current --- p.31 === Chapter 2.3.1. --- Enzymatic Dissociation of Coronary Artery Smooth Muscle Cells --- p.31 === Chapter 2.3.2. --- Electrophysiological Measurement --- p.31 === Chapter 2.4. --- DPPH Free Radical Scavenging Assay --- p.31 === Chapter 2.5. --- Solutions and Drugs --- p.32 === Chapter 2.5.1. --- "Drugs, Chemicals and Enzymes" --- p.32 === Chapter 2.5.2. --- Solutions Used in Force Measurement --- p.34 === Chapter 2.6. --- Statistical Analysis --- p.34 === Chapter Chapter III - --- Tamoxifen-Induced Endothelial Nitric Oxide-Dependent Relaxation in Porcine Coronary Arteries via Ouabain- and BaCl2-Sensitive Mechanisms === Chapter 3.1. --- Abstract --- p.35 === Chapter 3.2. --- Introduction --- p.36 === Chapter 3.3. --- Methods and Materials --- p.37 === Chapter 3.3.1. --- Vessel Preparation --- p.37 === Chapter 3.3.2. --- Isometric Force Measurement --- p.38 === Chapter 3.3.3. --- In situ Endothelial [Ca2+]i Imaging --- p.39 === Chapter 3.3.4. --- Chemicals --- p.40 === Chapter 3.3.5. --- Data Analysis --- p.40 === Chapter 3.4. --- Results --- p.41 === Chapter 3.4.1. --- Relaxant Responses --- p.41 === Chapter 3.4.2. --- Effects of Inhibitors of NO-Dependent Relaxation --- p.41 === Chapter 3.4.3. --- Effects of Putative K+ Channel Blockers and Ouabain --- p.41 === Chapter 3.4.4. --- "Effects of Ouabain, Removal of Extracellular K+ Ions and BaCI2" --- p.42 === Chapter 3.4.5. --- SNP-Induced Relaxation --- p.42 === Chapter 3.4.6. --- Effects of Actinomycin D and Cycloheximide --- p.42 === Chapter 3.4.7. --- Relaxant Effect of 17β-Estradiol --- p.43 === Chapter 3.4.8. --- Effects on Endothelial [Ca2+]i in Isolated Coronary Arteries With Endothelium --- p.43 === Chapter 3.5. --- Discussion --- p.53 === Chapter Chapter IV - --- Endothelium-Independent Relaxation to Raloxifene in Porcine Coronary Arteries === Chapter 4.1. --- Abstract --- p.57 === Chapter 4.2. --- Introduction --- p.58 === Chapter 4.3. --- Methods and Materials --- p.59 === Chapter 4.3.1. --- Vessel Preparation --- p.59 === Chapter 4.3.2. --- Isometric Force Measurement --- p.60 === Chapter 4.3.3. --- Electrophysiological Measurement of BKCa Current --- p.61 === Chapter 4.3.3.1. --- Enzymatic Dissociation of Coronary Artery Smooth Muscle --- p.61 === Chapter 4.3.3.2. --- Electrophysiological Measurement --- p.62 === Chapter 4.3.4. --- Chemicals --- p.63 === Chapter 4.3.5. --- Data Analysis --- p.63 === Chapter 4.4. --- Results --- p.64 === Chapter 4.4.1. --- Effect of Raloxifene on Agonist-Induced Contractions --- p.64 === Chapter 4.4.2. --- Role of Endothelium --- p.64 === Chapter 4.4.3. --- Effect of ER Antagonist --- p.65 === Chapter 4.4.4. --- Effect of Putative K+ Channel Blockers --- p.65 === Chapter 4.4.5. --- Effect of Elevated Extracellular K+ Concentrations --- p.65 === Chapter 4.4.6. --- Effects of Raloxifene on BKCa Current --- p.65 === Chapter 4.5. --- Discussion --- p.75 === Chapter Chapter V - --- Therapeutic Concentrations of Raloxifene Augment Bradykinin Mediated Nitric Oxide-Dependent Relaxation in Porcine Coronary Arteries === Chapter 5.1. --- Abstract --- p.78 === Chapter 5.2. --- Introduction --- p.79 === Chapter 5.3. --- Methods and Materials --- p.80 === Chapter 5.3.1. --- Vessel Preparation --- p.80 === Chapter 5.3.2. --- Isometric Force Measurement --- p.80 === Chapter 5.3.3. --- In situ Endothelial [Ca2+]i Imaging --- p.81 === Chapter 5.3.4. --- Free Radical Scavenging Assay --- p.82 === Chapter 5.3.5. --- Chemicals --- p.83 === Chapter 5.3.6. --- Data Analysis --- p.83 === Chapter 5.4. --- Results --- p.84 === Chapter 5.4.1. --- Relaxation to Bradykinin --- p.84 === Chapter 5.4.2. --- Effect of Raloxifene on Bradykinin-Induced Relaxation --- p.84 === Chapter 5.4.3. --- Effect of Raloxifene on Relaxation Induced by Substance P and --- p.85 === Chapter 5.4.4. --- Effect of Estrogen on Bradykinin-Induced Relaxation --- p.85 === Chapter 5.4.5. --- Effect of Raloxifene on Sodium Nitroprusside-Induced Relaxation --- p.86 === Chapter 5.4.6. --- Free Radical Scavenging Effect --- p.86 === Chapter 5.4.7. --- Raloxifene Augmentation of Bradykinin-Stimulated Endothelial [Ca2+]i --- p.86 === Chapter 5.5. --- Discussion --- p.99 === Chapter Chapter VI - --- "Cilnidipine, a Slow-Acting Ca2+ Channel Blocker, Induces Relaxation in Porcine Coronary Arteries: Role of Endothelial Nitric Oxide and [Ca2+]i" === Chapter 6.1. --- Abstract --- p.102 === Chapter 6.2. --- Introduction --- p.103 === Chapter 6.3. --- Methods and Materials --- p.104 === Chapter 6.3.1. --- Vessel Preparation --- p.104 === Chapter 6.3.2. --- Isometric Force Measurement --- p.105 === Chapter 6.3.3. --- In situ Endothelial [Ca2+]i Imaging --- p.106 === Chapter 6.3.4. --- Free Radical Scavenging Assay --- p.107 === Chapter 6.3.5. --- Chemicals --- p.108 === Chapter 6.3.6 --- Data Analysis --- p.108 === Chapter 6.4. --- Results --- p.108 === Chapter 6.4.1. --- Relaxant Responses --- p.108 === Chapter 6.4.2. --- Role of the Endothelium --- p.109 === Chapter 6.4.3. --- Effect of Inhibitors of NO-Dependent Relaxation --- p.109 === Chapter 6.4.4. --- Effect of Indomethacin and w-conotoxin --- p.110 === Chapter 6.4.5. --- Effect of Cilnidipine on Sodium Nitroprusside-Induced Relaxation --- p.110 === Chapter 6.4.6. --- Effects on Endothelial [Ca2+]i in Isolated Endothelium-Intact Coronary Arteries --- p.110 === Chapter 6.4.7. --- Free Radical Scavenging Effect --- p.110 === Chapter 6.5. --- Discussion --- p.120 === Chapter Chapter VII - --- General Summary --- p.123 === References --- p.128