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Endothelial dysfunction following denervation in bovine coronary arteries

O'Keefe, Peter Andrew; (1997) Endothelial dysfunction following denervation in bovine coronary arteries. Doctoral thesis (Ph.D.), University College London (United Kingdom). Green open access

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Transplanted hearts develop a diffuse, aggressive, atypical coronary arterial occlusive disease. Its high prevalence prompted investigation of the effect(s) of denervation on coronary arterial endothelial function using a bovine model. Other potentially injurious influences on coronary arterial endothelium were excluded, permitting the study of the effects of denervation in isolation. A series of randomised, controlled experiments were undertaken to investigate the effect of denervation on: 1. plasma endothelin concentrations. 2. endothelin-1 binding to coronary arteries. 3. the response of the coronary vasculature to endothelin-1 infusion. 4. the response of the coronary vasculature to calcitonin gene-related peptide infusion. 5. nitric oxide synthase activity in coronary arteries, as assessed by infusing endothelium-dependant vasodilators and a specific nitric oxide synthase inhibitor. 6. the production of intimal hyperplasia following a controlled coronary injury. In all groups, resting coronary vascular resistance was elevated following cardiac denervation. There was no effect of cardiac denervation on plasma endothelin-1 concentrations, nor on the coronary vascular response to calcitonin gene-related peptide infusion. Endothelin-1 binding to coronary arteries was significantly up-regulated, and this correlated with increased sensitivity to infused endothelin-1 suggesting an increase in the number of and/or affinity of endothelin receptors. Nitric oxide synthase activity appears to be increased in denervated coronary arteries, possibly in order to counteract a significant vasoconstrictive influence: the enzyme is more productive of nitric oxide, but has less reserve for further increase in production, and may be of a different isoform as it displays different characteristics when blocked with a specific inhibitor and re-stimulated with endothelium-dependent vasodilators. Both denervated and normally innervated coronary ateries respond to a significant coronary injury by intimal hyperplasia, but there were no characterisable differences in behaviour in the small number of samples studied.

Type: Thesis (Doctoral)
Qualification: Ph.D.
Title: Endothelial dysfunction following denervation in bovine coronary arteries
Open access status: An open access version is available from UCL Discovery
Language: English
Additional information: Thesis digitised by ProQuest.
Keywords: (UMI)AAI10106599; Health and environmental sciences
URI: https://discovery.ucl.ac.uk/id/eprint/10102007
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