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A role of ATP in modulating vasomotion during hypoxia in umbilical cord blood vessels

To, Wilson King Lim (2012)
Ph.D. thesis, University of Birmingham.

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Previous studies have associated intracellular calcium ([Ca2+]i) oscillations in vascular smooth muscle cells (SMC) with vasomotion in multiple species. In normal and pre-eclamptic pregnancies, there is strong evidence to suggest that the intrauterine environment is hypoxic. The aim of this study was to investigate whether ATP and [Ca2+]i oscillations play a role in modulating vasomotion during hypoxia in human umbilical blood vessels.

The results obtained from in vitro studies using firefly luciferase assay and quinacrine staining indicated that human umbilical artery and vein endothelial cell (HUAEC, HUVEC respectively) constitutively released ATP and, in HUVEC at least, the release was accentuated by hypoxia (7.6 mmHg O2, 30 min). This release is dependent on the PI3K/ROCK pathway, and on normal vesicular transport. Further, application of ATP to human umbilical artery SMC induced dose-dependent [Ca2+]i oscillations, which was mediated by P2Y4 receptor. Moreover, ex vivo data from freshly isolated umbilical artery rings showed that acute hypoxia increased the frequency of vasomotion.

It is therefore proposed that the findings of the present study is important in the understanding of the behaviour of human umbilical vessels in normal pregnancy, but may also have implications in the pathophysiology of complicated pregnancy such as pre-eclampsia.

Type of Work:Ph.D. thesis.
Supervisor(s):Marshall, Janice
School/Faculty:Colleges (2008 onwards) > College of Medical & Dental Sciences
Department:School of Clinical and Experimental Medicine
Subjects:RG Gynecology and obstetrics
Institution:University of Birmingham
ID Code:3313
This unpublished thesis/dissertation is copyright of the author and/or third parties. The intellectual property rights of the author or third parties in respect of this work are as defined by The Copyright Designs and Patents Act 1988 or as modified by any successor legislation. Any use made of information contained in this thesis/dissertation must be in accordance with that legislation and must be properly acknowledged. Further distribution or reproduction in any format is prohibited without the permission of the copyright holder.
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