Chan Hoi Yun. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2001. / Includes bibliographical references (leaves 131-144). / Abstracts in English and Chinese. / DECLARATION --- p.i / ACKNOWLEDGMENTS --- p.ii / ABBREVIATIONS --- p.iii / ABSTRACT IN ENGLISH --- p.v / ABSTRACT IN CHINESE --- p.viii / CONTENTS --- p.xi / Chapter Chapter 1 --- Introduction / Chapter 1.1. --- Steroid Hormones --- p.1 / Chapter 1.1.1. --- Synthesis of estrogens and progesterone --- p.1 / Chapter 1.2. --- Cellular Mechanisms of Female Steroid Hormones --- p.5 / Chapter 1.2.1. --- Genomic actions of female steroid hormones --- p.5 / Chapter 1.2.2. --- Non-genomic actions of female steroid hormones --- p.7 / Chapter 1.2.3. --- Estrogen antagonists --- p.7 / Chapter 1.2.3.1. --- Classification of estrogen antagonists --- p.7 / Chapter 1.2.3.2. --- Mechanisms of estrogen antagonists --- p.9 / Chapter 1.3. --- Chronic (genomic) Effects of 17β-Estradiol and Progesterone --- p.10 / Chapter 1.3.1. --- Effects of lipid metabolism --- p.10 / Chapter 1.3.2. --- Effects on cell proliferation --- p.11 / Chapter 1.3.3. --- Effects on endothelial cells --- p.12 / Chapter 1.4. --- Acute Effects of 17β-Estradiol and Progesterone --- p.13 / Chapter 1.4.1. --- Role of endothelium in 17β-estradiol or progesterone Relaxation --- p.13 / Chapter 1.4.2. --- Involvement of plasma membrane estrogen receptors --- p.14 / Chapter 1.4.3. --- Role of Ca2+ and K+ channel in estrogen relaxation --- p.14 / Chapter 1.4.4. --- Interaction with vasoconstrictors --- p.15 / Chapter 1.4.5. --- Interaction with endothelium-dependent dilators --- p.16 / Chapter 1.4.6. --- Interaction with adrenergic response --- p.17 / Chapter 1.5. --- Clinical Studies --- p.19 / Chapter 1.6. --- Therapeutic Values of Estrogen and Progesterone --- p.20 / Chapter 1.7. --- Objectives of the Present Study --- p.22 / Chapter Chapter 2 --- Method and Materials / Chapter 2.1. --- Tissue Preparation --- p.25 / Chapter 2.1.1. --- "Preparation of the rat aorta, mesenteric artery and carotid Artery" --- p.25 / Chapter 2.1.2. --- Removal of the functional endothelium --- p.26 / Chapter 2.2. --- Organ Bath Set-up --- p.26 / Chapter 2.3. --- Force Measurement --- p.28 / Chapter 2.3.1. --- Vascular action of 17β-estradiol and progesterone --- p.29 / Chapter 2.3.1.1. --- Role of endothelium/nitric oxide in 17β-estradiol- or progesterone-induced relaxation --- p.29 / Chapter 2.3.1.2. --- Role of inducible nitric oxide in progesterone-induced relaxation --- p.30 / Chapter 2.3.1.3. --- Effect of estrogen receptor inhibitor on 17β-estradiol- induced relaxation --- p.30 / Chapter 2.3.1.4. --- Interaction between progesterone and 17β-estradiol --- p.31 / Chapter 2.3.1.5. --- Effect of 17β-estradiol on protein kinase C-mediated contraction --- p.31 / Chapter 2.3.1.6. --- Synergistic interaction between β-adrenoceptor agonists and 17β-estradiol --- p.32 / Chapter 2.4. --- Porcine Coronary Artery Experiments --- p.33 / Chapter 2.4.1. --- Vessel preparation --- p.33 / Chapter 2.4.2. --- Force measurement --- p.33 / Chapter 2.4.3. --- Experimental protocol --- p.34 / Chapter 2.4.3.1. --- Effect of physiological level of 17β-estradiol on β- adrenoceptor agonist-induced relaxation --- p.34 / Chapter 2.4.3.2. --- Effect of physiological level of 17β-estradiol on phosphodiesterase inhibitor-induced relaxation --- p.34 / Chapter 2.5. --- Ovariectomy --- p.35 / Chapter 2.5.1. --- Method of ovariectomy --- p.35 / Chapter 2.5.2. --- Preparation of blood vessels --- p.36 / Chapter 2.5.3. --- Experimental protocols --- p.38 / Chapter 2.5.3.1. --- Effect of ovariectomy on contractility of rat carotid arteries --- p.38 / Chapter 2.5.3.2. --- Effect of ovariectomy on relaxation of rat carotid arteries --- p.38 / Chapter 2.6. --- Chemicals and Solutions --- p.39 / Chapter 2.7. --- Statistical Analysis --- p.42 / Chapter Chapter 3 --- Results / Chapter 3.1. --- Role of Endothelium/Nitric Oxide in 17β-Estradiol- and Progesterone-induced Relaxations --- p.43 / Chapter 3.1.1. --- Relaxant response of 17β-estradiol --- p.43 / Chapter 3.1.2. --- Effects of inhibitors of nitric oxide activity on 17β- estradiol-induced relaxation --- p.46 / Chapter 3.1.3. --- Relaxant response of progesterone --- p.46 / Chapter 3.1.4. --- Effects of inhibitors of nitric oxide activity on progesterone-induced relaxation --- p.50 / Chapter 3.2. --- Effect of Estrogen Receptor Inhibitor on 17β-Estradiol- induced Relaxation --- p.56 / Chapter 3.3. --- Interaction between Progesterone and 17β-Estradiol --- p.56 / Chapter 3.4. --- Effect of Female Sex Steroid Hormones on Protein Kinase C-mediated Contraction --- p.59 / Chapter 3.4.1. --- Effect of 17β-estradiol on phorbol ester-induced contraction --- p.59 / Chapter 3.4.2. --- Effect of progesterone on phorbol ester-induced contraction --- p.59 / Chapter 3.5. --- Effects of β-adrenoceptor Agonists on 17β-Estradiol- induced Relaxations --- p.62 / Chapter 3.5.1. --- Effect of isoproterenol on 17β-estradiol-induced relaxation --- p.62 / Chapter 3.5.2. --- Role of endothelium/nitric oxide on the isoproterenol potentiation of 17β-estradiol-induced relaxation --- p.63 / Chapter 3.5.3. --- Role of cyclic AMP on isoproterenol-enhancement of 17β- estradiol-induced relaxation --- p.69 / Chapter 3.5.4. --- Effects of β-adrenoceptor antagonists --- p.69 / Chapter 3.6. --- Effects of Physiological Concentration of 17β-EstradioI onβ-adrenoceptor Agonists-induced Relaxationsin Porcine Coronary Artery --- p.77 / Chapter 3.6.1. --- Effect of 17β-estradiol on isoproterenol-induced relaxations --- p.77 / Chapter 3.6.2. --- Effect of 17β-estradiol on fenoterol-induced relaxations --- p.11 / Chapter 3.6.3. --- Effect of 17β-estradiol on dobutamine-induced relaxations --- p.81 / Chapter 3.6.4. --- Effect of 17β-estradiol on IBMX-induced relaxation --- p.86 / Chapter 3.7. --- Effect of Ovariectomy on the Vascualr Reactivity --- p.88 / Chapter 3.7.1. --- Effect of ovariectomy on the contractile activity of rat carotid artery --- p.88 / Chapter 3.7.1.1. --- Effect of ovariectomy on phenylephrine-induced contraction --- p.88 / Chapter 3.7.1.2. --- Effect of ovariectomy on U46619-induced contraction --- p.96 / Chapter 3.7.1.3. --- Effect of ovariectomy on high K+- induced contraction --- p.102 / Chapter 3.7.1.4. --- Effect of ovariectomy on acetylcholine-induced relaxation --- p.106 / Chapter Chapter 4 --- Discussions / Chapter 4.1. --- Role of Endothelium/Nitric oxide in 17β-Estradiol- and Progesterone-induced Relaxations --- p.110 / Chapter 4.2. --- Effect of Estrogen Receptor Inhibitor on 17β-Estradiol- induced Relaxation --- p.113 / Chapter 4.3. --- Interaction between Progesterone and 17β-Estradiol --- p.114 / Chapter 4.4. --- Effects of Female Sex Steroid Hormones on Protein Kinase C-mediated Contraction --- p.115 / Chapter 4.5. --- Effects of β-Adrenoceptor Agonists on 17β-Estradiol- induced Relaxations --- p.116 / Chapter 4.6. --- Effects of 17β-Estradiol on β-Adrenoceptor Agonists- induced Relaxations in Porcine Coronary Artery --- p.121 / Chapter 4.7. --- Effect of Ovariectomy on the Vascular Reactivity --- p.125 / Chapter 4.8. --- Conclusions --- p.129 / References --- p.131 / Publications --- p.145

The following thesis will describe the investigation of the effect of nifedipine (a calcium antagonist) on the Doppler flow velocity waveform of the umbilical artery. The thesis is divided into two parts. The first section is a literature review of the three main aspects of the thesis namely: 1. The uteroplacental circulation in humans and the pathophysiology related to this circulation in hypertension and intrauterine growth retardation (IUGR). 2. The biokinetics of nifedipine and a review of the experiments that have been performed using the drug in human and animal models. 3. The principles of Doppler ultrasound and the literature pertaining to its use in the study of the uteroplacental circulation. The second part of the thesis is devoted to the effect of nifedipine on fetal umbilical artery Doppler waveform analysis. In the first ·stage of the investigation the effect of the drug on hypertensive mothers has been examined, and in the second stage the effect on fetuses that have an increased resistance index of the umbilical artery Doppler waveform.