Chronic Hypoxia Decreases Response to Central Chemoreceptor Stimulation in the Nucleus Tractus Solitarius (NTS)

One hallmark of acclimatization to chronic hypoxia (CH) is hyperventilation and a lower arterial carbon dioxide (CO ₂ ) level. These effects persist upon return to normoxia, suggesting a change in the regulation of CO ₂ during CH. We tested the hypothesis that plasticity in one central chemoreceptor site, the NTS, contributes to altered CO ₂ regulation in CH. In urethane-anesthetized rats, we stimulated chemoreceptors in the NTS by a unilateral microinjection of acetazolamide (ACZ, 1 nl of 0.3 µM), to produce focal acidosis. The product of rectified, integrated phrenic nerve amplitude and frequency (Phr) was measured 30 min after ACZ in normoxic control (N; n=5) and CH rats (n=5). ACZ increased Phr significantly more in N rats than CH rats (N=263±14%; CH=83±18%; p<0.001). ACZ in adjacent brainstem regions had no effect on Phr. All rats showed the capacity to increase Phr to a 10% inspired CO ₂ challenge following ACZ, suggesting that the dose of ACZ did not produce a maximal phrenic response. These results indicate plasticity in chemosensitivity in the NTS but they cannot easily explain the lower CO ₂ set point with CH.