Role of HIF and Prolyl-hydroxylase enzymes in ventilatory acclimatisation to hypoxia.

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Oxygen is essential for most forms of life. Even brief periods without oxygen can cause serious tissue damage or death. In humans the supply of oxygen to tissues is provided by the coordinated operation of lungs, heart & blood supply. The effectiveness with which the lungs load oxygen into the blood is monitored by oxygen sensors located close to major arteries (arterial chemoreceptors). If the body is subject to low levels of oxygen (hypoxia) for prolonged periods of time these chemoreceptors become progressively more sensitive to the lack of oxygen and promote a sustained increase in breathing. This process, called ventilatory acclimatisation, helps us to adapt to changes in environmental oxygen availability such as occur when we go to altitude. Indeed this is one of a number of adaptations that are essential for anyone attempting the assent of very high mountains. Similar changes also occur in some disease states but under these circumstances the effects of enhanced chemoreceptor activity are not always desirable. Our research therefore seeks to understand the mechanisms responsible for ventilatory acclimatisation. In particular we wish to test the hypothesis that oxygen dependent control of gene expression, a process very similar to that which gives rise to increase in the number of red blood cells in hypoxia, also controls chemoreceptor sensitivity.