Investigating the role of nitric oxide clones in cardiovascular conditions

Arif, Sayqa (2014). Investigating the role of nitric oxide clones in cardiovascular conditions. University of Birmingham. Ph.D.

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Abstract

Previously thought to be inert, nitrite is now deemed to be an important endogenous source of nitric oxide (NO), particularly during hypoxia and ischaemia. Largely animal and some limited human studies propose a role for nitrite in ‘hypoxic vasodilatation’ and ischaemia-reperfusion injury.

One study explores the effect of systemic nitrite infusion on cardiac and peripheral haemodynamic parameters in healthy subjects, during normoxia and hypoxia. Despite a lack of observed effects in healthy subjects, a study performed in patients with heart failure during normoxia demonstrated favourable haemodynamic effects on cardiac output, albeit at high doses of nitrite. In patients undergoing coronary artery bypass surgery, low dose nitrite infusion afforded protection against ischaemia-reperfusion injury. Several mechanisms of nitrite reduction to NO have been described and remain to be fully elucidated. The role of one of these putative mechanisms, namely mitochondrial aldehyde dehydrogenase (ALDH2) was explored during normoxia and hypoxia. Ex vivo human vascular ring studies confirmed ALDH2 as an important nitrite reductase, in contrast to in vivo observations in the forearm vasculature, suggesting that numerous mechanisms are involved in vivo which are harder to isolate. Furthermore, this hypoxia vasodilatory role was not replicated in with GTN in the human forearm vasculature.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

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