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 almost-equal-to 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 [H-3]dopamine from its natural precursor [H-3]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 [H-3]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 [H-3]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 [H-3]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.