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

D. R. McCrimmon, J. A. Dempsey, E. B. Olson

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14 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)522-528
Number of pages7
JournalJournal of Applied Physiology Respiratory Environmental and Exercise Physiology
Issue number2
StatePublished - 1983

ASJC Scopus subject areas

  • Physiology
  • Endocrinology


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