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Thesis (doctoral)--Lund University, 1997. / Added t.p. with thesis statement inserted.

Thesis (doctoral)--Lund University, 1995. / Added t.p. with thesis statement inserted.

Thesis (doctoral)--Lund University, 1995. / Added t.p. with thesis statement inserted.

Le Gengyun. / Thesis submitted in: December 2002. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2003. / Includes bibliographical references (leaves 161-182). / Abstracts in English and Chinese. / Abstract --- p.i / Abbreviations --- p.v / Acknowledgements --- p.vii / Publications --- p.viii / Table of Contents --- p.ix / Chapter Chapter 1 --- INTRODUCTION --- p.1 / Chapter 1. --- Vasoconstrictors --- p.1 / Chapter 1.1 --- An overview of vascular smooth muscle contraction --- p.1 / Chapter 1.2 --- Strong and weak vasoconstrictors --- p.5 / Chapter 1.2.1 --- Mechanisms involved in TP receptor vasoconstriction --- p.6 / Chapter 1.2.1.1 --- Brief introduction to the TP receptor --- p.6 / Chapter 1.2.1.2 --- Second messenger systems --- p.6 / Chapter 1.2.1.3 --- G-protein-linked pathways --- p.7 / Chapter 1.2.1.3.1 --- G proteins --- p.7 / Chapter 1.2.1.3.2 --- G-protein-linked TP receptor signal transduction --- p.8 / Chapter 1.2.2 --- Mechanisms involved in α1-adrenoceptor vasoconstriction --- p.8 / Chapter 1.2.2.1 --- Brief introduction to the α1-adrenoceptor --- p.8 / Chapter 1.2.2.2 --- Second messenger systems --- p.9 / Chapter 1.2.2.3 --- G-protein-linked α-adrenoceptor signal transduction --- p.9 / Chapter 1.3 --- Prostanoid EP3 receptor agonists (weak vasoconstrictors) --- p.10 / Chapter 1.3.1 --- Prostanoids --- p.10 / Chapter 1.3.1.1 --- Biochemical characteristics of prostanoids --- p.10 / Chapter 1.3.1.1.1 --- Biosynthesis of prostanoids --- p.10 / Chapter 1.3.1.1.2 --- Metabolism of prostanoids --- p.11 / Chapter 1.3.1.2 --- Prostanoid receptors --- p.13 / Chapter 1.3.1.2.1 --- Structures --- p.13 / Chapter 1.3.1.2.2 --- Current Status of Classification --- p.14 / Chapter 1.3.1.2.3 --- Signal transduction --- p.16 / Chapter 1.3.1.2.4 --- Distribution --- p.18 / Chapter 1.3.1.2.5 --- Physiological functions --- p.18 / Chapter 2. --- Interactions between vasoconstrictors --- p.19 / Chapter 2.1 --- Cross-talk between G-protein-coupled receptors --- p.19 / Chapter 2.1.1 --- Cross-talk between different receptor families --- p.19 / Chapter 2.1.2 --- Cross-talk between subtypes of the same receptor family --- p.21 / Chapter 2.1.3 --- Cross-talk at the effector level --- p.23 / Chapter 2.2 --- Proposed pathways involved in synergistic interactions --- p.24 / Chapter 2.2.1 --- Rho and Rho-associated kinase --- p.24 / Chapter 2.2.1.1 --- Rho family and its identification --- p.24 / Chapter 2.2.1.2 --- Mechanism(s) of Rho contribution in vasoconstriction --- p.25 / Chapter 2.2.1.3 --- Interactions between Rho and other pathways --- p.26 / Chapter 2.2.2 --- Receptor tyrosine kinases --- p.29 / Chapter 2.2.2.1 --- RTK family --- p.29 / Chapter 2.2.2.2 --- Activation of RTKs --- p.29 / Chapter 2.2.2.3 --- Mechanism(s) of RTK contribution in vasoconstriction --- p.30 / Chapter 2.2.2.4 --- Interactions between RTKs and MAPKs --- p.31 / Chapter 2.2.3 --- Mitogen-activated protein kinase --- p.34 / Chapter 2.2.3.1 --- p38 MAPK --- p.35 / Chapter 2.2.3.2 --- JNK MAPK --- p.35 / Chapter 2.2.3.3 --- ERK MAPK --- p.36 / Chapter 2.2.3.4 --- Interactions between MAPK and GPCRs --- p.37 / Chapter Chapter 2 --- FORCE MEASUREMENT SYSTEM --- p.41 / Chapter 1. --- Introduction --- p.41 / Chapter 2. --- Materials --- p.41 / Chapter 2.1 --- Drugs --- p.41 / Chapter 2.2 --- Chemicals --- p.41 / Chapter 2.3 --- Solutions --- p.46 / Chapter 3. --- Methods --- p.46 / Chapter 3.1 --- Isolated smooth muscle preparations and organ bath set-up --- p.46 / Chapter 3.2 --- Data analysis --- p.47 / Chapter Chapter 3 --- VASOCONSTRICTORS AND THEIR INTERACTIONS --- p.48 / Chapter 1. --- Introduction --- p.48 / Chapter 2. --- Materials and Methods --- p.48 / Chapter 2.1 --- Materials --- p.48 / Chapter 2.2 --- Methods --- p.51 / Chapter 2.2.1 --- Isolated tissue preparations --- p.51 / Chapter 2.2.2 --- Experimental protocols --- p.51 / Chapter 2.2.3 --- Statistical analysis --- p.52 / Chapter 3. --- Results --- p.55 / Chapter 3.1 --- Typical vasoconstrictor profiles of agonists --- p.55 / Chapter 3.1.1 --- Sulprostone contraction --- p.55 / Chapter 3.1.2 --- U-46619 contraction --- p.55 / Chapter 3.1.3 --- Phenylephrine contraction --- p.56 / Chapter 3.2 --- Synergistic interactions between sulprostone and strong vasoconstrictors --- p.58 / Chapter 3.2.1 --- Enhancement of U-46619 response by sulprostone --- p.58 / Chapter 3.2.2 --- Enhancement of phenylephrine response by sulprostone --- p.58 / Chapter 3.2.3 --- Enhancement of sulprostone response by phenylephrine --- p.58 / Chapter Chapter 4 --- INVESTIGATION OF PATHWAYS INVOLVED IN EP3 AGONIST- INDUCED VASOCONSTRICTION --- p.64 / Chapter 1. --- Introduction --- p.64 / Chapter 2. --- Materials and methods --- p.65 / Chapter 2.1 --- Materials --- p.65 / Chapter 2.2 --- Methods --- p.65 / Chapter 2.2.1 --- Isolated tissue preparations --- p.65 / Chapter 2.2.2 --- Experimental protocols --- p.65 / Chapter 2.2.3 --- Statistical analysis --- p.69 / Chapter 3. --- Results --- p.70 / Chapter 3.1 --- Effects of tyrosine kinase inhibitors --- p.70 / Chapter 3.2 --- Effects of MAPK inhibitors --- p.82 / Chapter 3.2.1 --- Effects of MAPK inhibitors on U-46619 responses --- p.82 / Chapter 3.2.2 --- Effects of MAPK inhibitors on sulprostone responses --- p.91 / Chapter 3.2.3 --- Effects of MAPK inhibitors on phenylephrine responses --- p.100 / Chapter 3.3 --- Effects of Rho-kinase inhibitors --- p.104 / Chapter Chapter 5 --- TRANSFECTED CELL LINE SYSTEM --- p.111 / Chapter 1. --- Introduction --- p.111 / Chapter 2. --- Materials and methods --- p.114 / Chapter 2.1 --- Materials --- p.114 / Chapter 2.1.1 --- Plasmids and vectors --- p.114 / Chapter 2.1.2 --- Radioactive agents --- p.114 / Chapter 2.1.3 --- Chemicals --- p.114 / Chapter 2.1.4 --- Restriction digest enzymes --- p.115 / Chapter 2.1.5 --- "Culture media, buffers and solutions" --- p.115 / Chapter 2.1.5.1 --- Culture media / Chapter 2.1.5.2 --- Buffers and solutions --- p.115 / Chapter 2.2 --- Methods --- p.116 / Chapter 2.2.1 --- Transfected cell lines --- p.116 / Chapter 2.2.1.1 --- Subcloning of hEP3-1 receptor and hTP receptor cDNA --- p.116 / Chapter 2.2.1.1.1 --- Plasmid recovery / Chapter 2.2.1.1.2 --- Preparation of competent cells --- p.116 / Chapter 2.2.1.1.3 --- Transformation of competent cells --- p.117 / Chapter 2.2.1.1.4 --- Extraction of DNA by QIAGEN Plasmid Mini Kit --- p.117 / Chapter 2.2.1.1.5 --- Restriction enzymes digestion and dephosphorylation --- p.117 / Chapter 2.2.1.1.6 --- DNA recovery and ligation / Chapter 2.2.1.1.7 --- Positive recombinant DNA selection --- p.119 / Chapter 2.2.1.2 --- Cell culture --- p.119 / Chapter 2.2.1.3 --- Transient transfection of CHO cells --- p.121 / Chapter 2.2.1.4 --- Mesurement of adenylate cyclase activity --- p.121 / Chapter 2.2.1.4.1 --- Preparation of columns --- p.121 / Chapter 2.2.1.4.2 --- [3H]-cAMP assays --- p.122 / Chapter 2.2.1.5 --- Measurement of phospholipase C activity --- p.122 / Chapter 2.2.1.5.1 --- Preparation of columns --- p.123 / Chapter 2.2.1.5.2 --- [3H]-inositol phosphate assay --- p.123 / Chapter 2.2.2 --- Data analysis --- p.124 / Chapter 3. --- Results --- p.125 / Chapter 3.1 --- Subcloning of hEP3-1and hTPα receptor cDNA into expression vectors --- p.125 / Chapter 3.2 --- Measurement of cAMP and IP production in transfected CHO cells --- p.133 / Chapter 3.2.1 --- Effect of varying receptor cDNA concentration on agonist-stimulated [3H]-cAMP and [3H]-IP production in transiently transfected CHO cells --- p.133 / Chapter 3.2.2 --- Effect of agonists on intracellular [3H]-IP or [3H]-cAMP productionin CHO cells transfected with hTPα or hEP3-1 --- p.133 / Chapter 3.3 --- Summary --- p.134 / Chapter Chapter 6 --- GENERAL DISCUSSION AND CONCLUSIONS --- p.137 / Chapter 1. --- Vasoconstrictors and their interactions --- p.137 / Chapter 1.1 --- Vasoconstrictors --- p.137 / Chapter 1.2 --- Synergism --- p.138 / Chapter 2. --- Investigation of possible pathways --- p.140 / Chapter 2.1 --- Rho-associated kinase --- p.140 / Chapter 2.2 --- Receptor tyrosine kinase --- p.147 / Chapter 2.3 --- Mitogen-activated protein kinase (MAPK) --- p.151 / Chapter 3. --- Effect of vehicles --- p.155 / Chapter 4. --- Biochemical studies in transfected CHO cells --- p.157 / Chapter 5. --- Conclusions --- p.158 / Appendix I --- p.159 / Buffers and Solutions used in transfected system --- p.159 / Chapter 1. --- Buffers --- p.159 / Chapter 2. --- Solutions --- p.159 / REFERENCES --- p.161

Diss. (sammanfattning) Stockholm : Karol. inst., 2004. / Härtill 4 uppsatser.

xvii, 174 p. : ill. A print copy of this thesis is available through the UO Libraries. Search the library catalog for the location and call number. / During acute altitude exposure, humans maintain higher skin temperature and lower core body temperature. However, the role of cutaneous vascular regulation in these thermoregulatory differences is unclear. Therefore, the purpose of these studies was to investigate the impact of altitude exposure on reflex control of skin blood flow and core temperature during cold exposure. In Chapter IV, the effects of hypoxia and hypocapnia on cutaneous vasoconstriction during mild cold exposure were investigated. We found that hypoxia stimulates cutaneous vasodilation in men whereas skin blood flow is unaltered in women. However, during whole body cooling skin blood flow is upward shifted in both sexes. The development of hypocapnia does not affect the vascular response to hypoxia in either sex, but reduces the magnitude of cutaneous vasoconstriction during cold exposure by 50% in women. In Chapter V, we studied the timecourse of α-adrenergic blockade by yohimbine in the cutaneous circulation and how the duration of cold exposure modulates cotransmitter-mediated vasoconstriction during cold stress. We found that yohimbine produces functional α-adrenergic blockade within 30 minutes of initial delivery and completely abolishes reflex cutaneous vasoconstriction during mild cold stress. This latter finding was surprising, and an additional protocol demonstrated that cotransmitter-mediated vasoconstriction only participates in the vascular response to cold stress when the exposure is more prolonged. In Chapter VI, the effects of hypoxia on cutaneous vasoconstrictor mechanisms and core cooling rate were tested during more prolonged and severe cold stress. In contrast to our findings during brief cold exposure, we showed that cutaneous vasoconstriction during prolonged cold stress is potentiated by hypoxia and abolishes hypoxic vasodilation. Moreover, increased cotransmitter-mediated vasoconstriction appears to account for this response. Hypoxia had no effect on core cooling rate during severe cold exposure. The selective potentiation of cotransmitter-mediated vasoconstriction observed during hypoxia in Chapter VI provided the basis for Chapter VII. This study was designed to test the effect of hypoxia on cutaneous vascular responsiveness to peripherally stimulated sympathetic vasoconstriction. The results demonstrated that α-adrenergic vasoconstrictor transduction is not affected by hypoxia, and that stimulation of adrenergic nerves with tyramine does not elicit cotransmitter-mediated vasoconstriction in skin. / Adviser: John R. Halliwill