Bhagat, Kiran; (1997) The effects of inflammatory mediators on endothelial and smooth muscle function in vivo. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

Inflammation of the blood vessel wall has been implicated in the pathogenesis of diseases as apparently diverse as septic shock, unstable angina and acute myocardial infarction. Most studies exploring the effects of inflammatory signals on vascular reactivity have been undertaken in animals or using human cells or tissues in vitro. However, it is recognised that there is considerable species variation in the mechanisms of inflammation and that the results of studies in vitro differ from those undertaken in vivo. This thesis describes the development and application of a novel approach to administer inflammatory mediators to volunteers in vivo in order to determine any changes in vascular reactivity seen. A single vessel was isolated from the rest of the circulation and exposed to inflammatory agents. The change in the reactivity was then assessed with the vessel in its normal physiological environment. Bacterial endotoxin and certain pro-inflammatory cytokines were used to initiate an inflammatory response. Changes in endothelial and smooth muscle function were assessed and the contribution of nitric oxide or prostanoids determined. In some studies surgical biopsies were taken in order to characterise the molecular basis of the pharmacological changes. Parallel experiments were also undertaken to study the effects of inflammation in a variety of in vitro systems, using human cells and tissues.

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