Physiological And Pathological Responses To Hypoxia And High Altitude

The appearance of photosynthetic organisms about 3 billion years ago increased the partial pressure of oxygen (PO2) in the atmosphere and enabled the evolution of organisms that use glucose and oxygen to produce ATP by oxidative phosphorylation. Hypoxia is commonly defined as the reduced availability of oxygen in the tissues produced by different causes, which include reduction of atmospheric PO2 as in high altitude, and secondary to pathological conditions such as sleep breathing and pulmonary disorders, anemia, and cardiovascular alterations leading to inadequate transport, delivery, and exchange of oxygen between capillaries and cells. Nowadays, it has been shown that hypoxia plays an important role in the genesis of several human pathologies including cardiovascular, renal, myocardial and cerebral diseases in fetal, young and adult life. Several mechanisms have evolved to maintain oxygen homeostasis. Certainly, all cells respond and adapt to hypoxia, but only a few of them can detect hypoxia and initiate a cascade of signals intended to produce a functional systemic response. In mammals, oxygen detection mechanisms have been extensively studied in erythropoietin-producing cells, chromaffin cells, bulbar and cortical neurons, pulmonary neuroepithelial cells, smooth muscle cells of pulmonary arteries, and chemoreceptor cells. While the precise mechanism underpinning oxygen, sensing is not completely known several molecular entities have been proposed as possible oxygen sensors (i.e. Hem proteins, ion channels, NADPH oxidase, mitochondrial cytochrome oxidase). Remarkably, cellular adaptation to hypoxia is mediated by the master oxygen-sensitive transcription factor, hypoxia-inducible factor-1, which can induce up-regulation of different genes to cope the cellular effects related to a decrease in oxygen levels. Short-term responses to hypoxia included mainly chemoreceptor-mediated reflex ventilatory and hemodynamic adaptations to manage the low oxygen concentration while more prolonged exposures to hypoxia can elicit more sustained physiological responses including switch from aerobic to anaerobic metabolism, vascularization, and enhancement of blood O2 carrying capacity. The focus of this research topic is to provide an up-to-date vision on the current knowledge on oxygen sensing mechanism, physiological responses to acute or chronic hypoxia and cellular/tissue/organ adaptations to hypoxic environment.