Effect of catecholamine depletion on ventilatory control in unanesthetized normoxic and hypoxic rats

The ventilatory effects produced by pharmacological depletion of endogenous catecholamines were examined during air-breathing eupnea and acclimatization to hypoxia (fraction of inspired O₂ equals 0.12-0.125) in awake unrestrained rats. Biochemical analysis confirmed that the administration of α-methyl-p-tyrosine (AMT) reduced brain and carotid body norepinephrine (NE) and dopamine (DA), whereas bis-(y-methyl-1-homopiperazinylthiocaronyl) disulfide (FLA-63) decreased NE only. Arterial blood gases and acid-base balance, minute ventilation, and O₂ consumption were measured in rats treated with one of the drugs or drug vehicles. Reproducibility of the measurements was documented for both within and between days. AMT (100 mg/kg ip and 50 mg/kg ip 5 or 24 h later) decreased brain catecholamines 50-60% but did not alter air-breathing eupnea or the acute (1 h) or sustained (5 and 24 h) ventilatory responses to hypoxia. AMT (8 injections of 80 mg·kg^-1·3 h^-1 ip) reduced brain and carotid body NE and DA 70-80% and elicited a sustained but variable hyperventilation and respiratory alkalosis in normoxia (-2.9 ± 1.6 Torr arterial PCO₂). The acute ventilatory response to hypoxia was unaltered. FLA-63 (25 mg/kg iv) decreased brain NE selectively by about 65% but did not alter ventilation during air-breathing eupnea nor during the acute response to hypoxia. These results indicated that a marked depletion of catecholamines was required to produce even a relatively small ventilatory effect and implicated NE and/or DA in a mild inhibition of breathing in the awake, intact rat. Neither NE nor DA appear to be required for mediation of ventilatory acclimatization to chronic hypoxia.