Oxygen and carbon dioxide in the regulation of respiration

When a sea-level resident ascends to a high altitude, his breathing immediately increases because of hypoxic stimulation of the peripheral chemoreceptors. In many species the aortic bodies are relatively unimportant in this response compared to the carotid bodies. When the subject stays at that altitude, his breathing increases progressively in the next few hours and days in a process termed ventilatory acclimatization and does not immediately return to control levels when hypoxia is terminated. Evidence is summarized indicating that this chronic process does not depend on the peripheral chemoreceptors or an initial respiratory alkalosis. Historical review indicates that the process of ventilatory acclimatization was initially attributed to renal excretion of plasma bicarbonate with development of a metabolic acidosis; but subsequent measurements indicated this process did not lower the arterial pH sufficiently to account for the ventilatory stimulation. More recently, ventilatory acclimatization has been attributed to accelerated removal of bicarbonate from the cerebrospinal fluid (CSF), producing a metabolic acidosis in the region of the medullary chemoreceptors; but still more recent observations indicate that this process, contrary to earlier observations, does not lower the CSF pH sufficiently to account for the ventilatory stimulation, either. Some other mechanism should be sought.