Effects of Chronic Hypoxia on Opioid Peptide and Catecholamine Levels and on the Release of Dopamine in the Rabbit Carotid Body

Carotid body catecholamine and opioid levels were measured in rabbits exposed for 8 days to an atmosphere of 11% O2 in N2 (Po2 of ∼ 80 mm Hg) and during an identical period of recovery, i.e., after 8 days of returning to the control normoxic atmosphere. Carotid bodies show a decrease in dopamine content at day 2. Thereafter, the levels of this biogenic amine increase progressively to peak at day 10, that is, 2 days after returning to a normoxic atmosphere. Finally, dopamine levels start to decrease and reach prehypoxic control levels at day 16, that is, after 8 days of recovery. In contrast, levels of native opioid peptides remain unchanged during the whole duration of the experiment, except for a decrease at day 2 of the hypoxic exposure. Levels of total opioid peptides are also below control values at day 2 of hypoxia, increase above control values on returning to a normoxic atmosphere (maximal levels at days 10‐12), and later decrease to reach prehypoxic levels at day 16. As a result of these changes the ratios of dopamine to opioid levels show a progressive increase from day 0 to day 10 of the experiment and then return to control prehypoxic values. Carotid bodies isolated from animals that have been exposed to hypoxia for 8 days synthesize [3H]dopamine from its natural precursor [3H]tyrosine at a rate of 175 pmol/mg of protein/h, which is about double the rate of synthesis found in the carotid bodies of control animals and those allowed to recover for 8 days. The release of [3H]‐dopamine induced by mild hypoxic stimuli and by a high external K+ concentration is greater in the carotid bodies isolated from animals hypoxic for 8 days than in those of control animals (catecholamine deposits were labeled by prior incubation with [3H]tyrosine); in contrast, the carotid bodies from chronically hypoxic animals exhibit an attenuated release response to intense hypoxic stimuli and to dinitrophenol. Stimulus‐induced release of [3H]dopamine by carotid bodies isolated from animals allowed to recover for 8 days is not different from that of control animals. Our results suggest that modifications in the proportions of neurotransmitters, as well as changes in the stimulus‐secretion coupling machinery in chemoreceptor cells, contribute to the adaptative responses seen in the carotid body during high altitude acclimatization.