To, Wilson King Lim (2012)
Ph.D. thesis, University of Birmingham.
Restricted to Repository staff only until 01 July 2015.
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.
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