Control of breathing

Abstract

Upon rapid ascent to high

altitude or acute exposure to hypoxia ventilation rises rapidly (the acute

hypoxic ventilatory response, initiated by the carotid bodies containing oxygen

sensors), followed immediately by a secondary roll-off that partly is caused by the hyperventilation-induced hypocapnia. When the hypoxia is sustained, ventilation starts to rise grad- ually within the next few hours, that, depending on the species and alti- tude (degree of hypoxia), may last from hours to months. This phenomenon is known as ventilatory acclimatization to high altitude (VAH). Many studies have shown that this ventilatory adaptation is not due to a gradual acidosis in blood or extracellular brainstem fluid bathing the central che- moreceptors. One of the most remarkable changes is a considerable increase in the ventilatory response to hypoxia that is manifest already after ~4 h and that may continue to augment during the next days–weeks. This adaptive change is thought to underlie VAH and is caused by many plastic morphological and biochemical changes in both the carotid bodies and the central nervous system. An important orchestrator of these plastic changes is the transcription factor, hypoxia inducible factor 1 (HIF-1) that induces the transcription of many genes encoding substances indis- pensable for the adaptation of the organism to sustained hypoxia. This chapter describes the most important of these and summarizes the state of the art on the mechanisms underlying the plastic changes in carotid bod- ies and central nervous system.