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].