E. Mulligan

Adaptive response of carotid body chemoreceptors to CO2.

Carotid body chemoreceptor responses to sudden changes in pETCO2 (end-tidal tracheal CO2 partial pressure) and paCO2 (arterial CO2 partial pressure) from one stable state to another at a constant level of PETO2 (end-tidal tracheal O2 partial pressure) and paO2 (arterial O2 partial pressure) were studied in 18 anesthetized cats. Chemoreceptor activity was recorded from single or pauci-fiber filaments of a cut sinus nerve. During a hypercapnic stimulus by CO2 inhalation the discharge rate rapidly increased to a peak and then adapted to a lower level in 20-30 s showing an overshoot in the response. Likewise, withdrawal of the hypercapnic stimulus was followed by an undershoot in chemoreceptor activity. Hypoxia decreased the latency of the response and increased the overshoot and stable state responses to hypercapnia. The responses to step paCO2 increases by blood perfusion were qualitatively similar but the latency and time to peak amplitude were shorter and the peak amplitude was larger at any given perfusate pO2. The stable state responses to a given paCO2 achieved by CO2 inhalation or by blood perfusion were similar. The transient overshoot and undershoot in the activity produced by the increase and decrease in paCO2 were blocked by acetazolamide, a carbonic anhydrase inhibitor. The results are best explained by postulating that in the carotid body tissue, H+ is generated from CO2 in one compartment in the presence of carbonic anhydrase and is transported to another containing the receptor site in a pO2 dependent way--a high pO2 attenuating and a low pO2 augmenting it.

Adrenergic mechanisms in oxygen chemoreception in the cat aortic body

Sixteen cats were studied to test the hypothesis that oxygen chemoreception in the cat aortic body is dependent on the beta-adrenergic mechanism. The chemoreceptor activity was measured from a few aortic chemoreceptor afferents in each cat, anesthetized with alpha-chloralose (60 mg X kg-1). Three types of experiments were conducted. Aortic chemoreceptor responses to steady-state hypoxia (PaO2 range, 100-30 Torr) were measured (a) before and during intravenous infusion of the beta-receptor agonist, isoproterenol (0.5 micrograms X kg-1) in nine spontaneously breathing cats, and (b) before and after intravenous injection of the beta-receptor antagonist, propranolol (1 mg X kg-1) in seven cats which were paralyzed and artificially ventilated. In the third category (c) the stimulatory effect of hypotension on aortic chemoreceptor activity was measured in six of the seven cats in group (b) before and after propranolol injection. Isoproterenol infusion only moderately stimulated aortic chemoreceptor activity. This stimulation was blocked by propranolol. However, propranolol did not attenuate aortic chemoreceptor responses to hypoxia or to hypotension. We conclude that the beta-receptor adrenergic mechanism does not mediate oxygen chemoreception in the cat aortic body.

Altered Function of Cat Carotid Body Chemoreceptors in Prolonged Hyperoxia

On thermodynamic grounds the mitochondrial redox catalysts are likely to be oxidized by molecular oxygen. Accordingly, their rates of auto-oxidation are enhanced by increasing oxygen pressure, generating oxygen radicals. These radicals are ordinarily removed by the protective enzymes such as Superoxide dismutase. Overproduction of the naturally occuring oxygen radicals during hyperoxia can overwhelm the enzymatic removal systems, resulting in a net accumulation of these free radicals (Fridovitch, 1983). Since oxygen chemoreception in the peripheral chemoreceptors depends on a reaction or interaction with oxygen, and since the chemosensory discharge continues to be suppressed by PO2 increases even in the hyperoxic range, we hypothesised that the chemoreceptor tissue may be specifically sensitive to oxygen radicals.