Abstract
The hypoxic ventilatory response (HVR) can be modulated by dopamine D 2-receptors (D 2-R) in both the carotid body arterial chemoreceptors and the nucleus tractus solitarius (NTS), the primary synapse site of carotid body afferents. We hypothesized that chronic hypoxia alters D 2-R gene expression to initiate changes in D 2-R modulation of the HVR and enhance ventilatory acclimatization to hypoxia. Thus, we used a competitive reverse transcription-polymerase chain reaction (RT-PCR) method to quantify changes in D 2-R mRNA levels in the rat carotid body and NTS after 0, 6, 12, 24, 48, or 168 h of hypobaric hypoxia ( P IO 2 =80 Torr). In the rostral NTS, hypoxia significantly increased D 2-R mRNA at all time points. In the caudal NTS, D 2-R mRNA levels initially increased in response to hypoxia and then significantly decreased to 71±5% and 71±6% of control after 48 and 168 h of hypoxia, respectively. In the carotid body, D 2-R mRNA levels significantly decreased to 59±2% of control after 48 h of hypoxia; however, they significantly increased to 274±22% of control after 168 h. These results suggest that changes in D 2-R mRNA in the arterial chemoreflex pathway and corresponding changes at the protein and signaling levels may contribute to the time-dependent changes in ventilation observed with chronic hypoxia. Specifically, decreased carotid body inhibition by D 2-R could increase the HVR after 2 days of hypoxia.
Published Version
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