Disease mechanisms which can be modelled with experimental hypoxia
Systemic hypoxic stress, as seen at high altitude or in a hypoxia chamber, leads to hypoxic pulmonary vasoconstriction and a large increase in pulmonary arterial pressure. Pulmonary arterial hypertension up to 66 mmHg systolic arterial pressure has been safely induced over weeks in healthy individuals by normobaric hypoxia [40]. Pulmonary arterial hypertension at altitude is not a disease per se, but it can cause a life-threatening condition if it progresses into high-altitude pulmonary edema. Studies in mountaineers have revealed that the vasoactive factors that are involved in the development of the hypoxic pulmonary vasoconstriction at altitude are also responsible for the pulmonary arterial hypertension in patients. Chronic sojourn at high altitude may eventually result in pulmonary arterial hypertension and, remodeling of the pulmonary vasculature and right heart failure.
Pulmonary arterial hypertension is caused by a disbalance between vasodilatory and vasoconstrictive factors. Relative to healthy individuals, patients with pulmonary hypertension have reduced levels of the key vasodilators nitric oxide (NO), its second messenger cGMP, and prostacyclin while vasoconstrictors endothelin-1 and thromboxane A2 are increased. Additionally, the production of reactive oxygen species is increased, which is caused by the induction of oxidase systems [62].