Time-dependent changes in dopamine D(2)-receptor mRNA in the arterial chemoreflex pathway with chronic hypoxia

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.