Adrenergic mechanisms and chemoreception in the carotid body of the cat and rabbit

Abstract

1. The effect of beta-adrenergic and dopaminergic agonists and antagonists on the chemoreceptor response to graded hypoxia and hypercapnia was tested in nineteen cats and ten rabbits anaesthetized either with chloralose-urethane or pentobarbitone sodium, paralysed with pancuronium bromide and artificially ventilated.2. The inhibitory action of dopamine was confirmed. The inhibition following intra-arterial bolus injection was blocked by haloperidol; dopamine then excited and this excitation was blocked with propranolol. Adrenaline or noradrenaline caused a transient inhibition followed by a marked excitation. The inhibition was blocked with haloperidol and the excitation blocked with propranolol or metoprolol. Isoprenaline excited without inhibition and this was blocked with propranolol or metoprolol.3. A novel finding was that the chemoreceptor response to hypoxia was markedly reduced or even abolished with propranolol or metoprolol. The response was enhanced with a constant infusion of isoprenaline, adrenaline or noradrenaline in proportion to the degree of hypoxia, an effect mimicked by raising CO(2). The chemoreceptor response to hypoxia was similarly enhanced by haloperidol and depressed by a constant infusion of dopamine in proportion to the degree of hypoxia.4. The effect of these drugs on the chemoreceptor response to hypercapnia was less constant. In the majority of tests the aminergic agonists and antagonists caused a parallel shift of the CO(2) response curves in the same direction as the O(2) response curves and by amounts proportional to the degree of hypoxia. In some tests these drugs caused a change in the slope of the CO(2) response curves but only if P(a, O2) was less than 60 mmHg.5. One interpretation of these results is that hypoxia exerts a presynaptic action, causing the release of noradrenaline and dopamine from Type I cells, and that these substances act upon aminergic receptors on the sensory fibre, causing a change in potential and discharge frequency proportional to the rates of dopamine and noradrenaline release.6. An additional or alternative interpretation is that O(2) and CO(2) (the latter most probably acting on intracellular pH) alter the sensitivity of the aminergic receptors to their agonists.