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Title: Distribution and function of the oestrogen receptor β in the cardiovascular system of the mouse
Author: Ness, Katrina Frances
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2005
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The aim of this thesis was to determine the distribution of ERs in the CVS and whether this was altered under pathophysiological conditions. We hypothesised that oestrogen acting through ERs modifies vascular function and contributes to regulation of blood pressure. Therefore, blood pressure and vascular function were assessed in female mice of different oestrogen status and the influence of ERβ determined by studying male ERβ knock-out (βERKO) mice and female WT mice treated with a novel ERβ antagonist. Immunoreactive ERβ was associated with nuclei of myocardial, endothelial (ETC) and vascular smooth muscle cells (VSMC) of the heart, aorta and mesenteric artery in both male and female wild type (WT) and βERKO mice. The distribution of ERβ in mouse models of atherosclerosis and myocardial infarction (MI) were not different to that of normal mice. Mean arterial blood pressure (MABP) measured in young and aged WT and βERKO mice, by implantation of a Millar catheter into the left carotid artery, was found to increase with age. However, there was no difference in MABP between βERKO and age- matched WT animals. MABP of female WT mice, as measured by radiotelemetry suggested that both endogenous and exogenous oestrogen increased MABP. Treatment of female mice with an ERβ antagonist resulted in an increase in MABP in sham ovx mice whilst MABP was reduced in mice which were of ovx+E. Mesenteric vessels isolated from sham ovx and ovx+E showed that chronic E treatment increased the sensitivity to PE. Treatment of sham ovx animals with an ER antagonist did not alter vascular function. Whilst treatment of ovx+E mice with the ERβ antagonist, led to a reduction in the sensitivity to PE and an increase in both endothelium- dependent and -independent vasodilatation.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available