In this thesis I have investigated the profile and significance of nitric oxide metabolites in two human models: 1) Across healthy human coronary and pulmonary vascular beds 2) In the peripheral venous blood from patients with type 1 diabetes mellitus. Chapters 1-3 offer a comprehensive background detailing issues of relevance to the rest of this work. Chapter 4 outlines precise methodological protocols and materials used. The results of the above clinical and laboratory studies are presented and discussed in Chapters 5 and 6. Chapter 7 attempts to summarise the results obtained, drawing together conclusions and highlighting perspectives for future research. I found that nitric oxide was dynamically metabolised across the heart and that the compartmentalisation of its metabolites between plasma and erythrocytes was driven primarily by the oxygen saturation of the blood. Study of the changes in coronary arterial diameter and flow in response to exercise and inhibition of nitric oxide generation suggested the presence of an endothelium derived hyperpolarising factor-like activity in the epicardial coronary arteries. Among patients with type 1 diabetes, blood levels of nitric oxide metabolites were generally lower compared to controls and lower in those with microvascular complications comparing to those without. Vessel relaxation experiments suggested the existence of a red blood cell-related vasodilating factor (RRVF) which was present in both diabetics and controls but exerted stronger vasodilator activity when erythrocytes from the former group were added to aortic ring preparations in a hypoxic tissue bath system ex vivo. Another novel finding was a positive correlation between this RBC-related vasodilator activity and HbAic which was stronger in that group of patients who were generally younger with shorter duration of disease.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:584479 |
| Date | January 2008 |
| Creators | Khalatbari, Afshin |
| Publisher | Cardiff University |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://orca.cf.ac.uk/55785/ |
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