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Title: The role of inorganic nitrite in the transport of nitric oxide in health and heart failure
Author: Maher, Abdul R.
ISNI:       0000 0004 2729 650X
Awarding Body: University of Birmingham
Current Institution: University of Birmingham
Date of Award: 2012
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The potential for nitric oxide (NO) metabolites (e.g. inorganic nitrite) to act as stable stores of “Transported Nitric Oxide” has excited huge interest due to the substantial potential therapeutic avenues. The prospect developing of a “silver bullet” that could target areas most in need of vasodilatation, by releasing NO in areas of hypoxia and ischaemia, could prove a massive advance in the treatment of vascular disease. In this thesis I examine the effects of nitrite infusion in both hypoxia and normoxia. I examine the effects both in health and heart failure, and investigate the potential roles of Nitric Oxide Synthase (NOS) and Xanthine Oxidase (XO) in mediating the reduction of nitrite. We found, and were the first to report in man, that intra-arterial infusions of nitrite had little effect upon the vasculature in high oxygen tension environments but led to significant vasodilatation during hypoxaemia. We found that patients suffering with Chronic Heart Failure responded differently to nitrite infusion to healthy controls, possibly as a result of differences in redox-stress. In healthy volunteers, at rest, neither NOS nor XO appeared to play a significant role in nitrite induced vasodilatation in normoxia and mild hypoxia. We found that vascular myoglobin contributes to the reduction of nitrite to nitric oxide and may play a role in prolonging the vasodilatation induced by nitrite infusion.
Supervisor: Not available Sponsor: British Heart Foundation
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: QH301 Biology ; RB Pathology ; RC Internal medicine ; RZ Other systems of medicine