The effect on carotid chemoreceptor afferents of oligomycin, an inhibitor of mitochondrial oxidative phosphorylation that does not affect energy conservation, was studied in 20 cats that were anesthetized, paralyzed, and artificially ventilated. Responses of single or a few chemoreceptor afferents to changes in arterial O2 tension (PaO2) at constant arterial CO2 tension were recorded. In addition, responses to nicotine, cyanide, and antimycin A or carbonyl cyanide p-tri-fluoromethoxyphenylhydrazone (FCCP) were tested in normoxia. Oligomycin (50-500 microgram) was administered by close intra-arterial injection, and the same tests were repeated at timed intervals. Initially, oligomycin caused vigorous stimulation of carotid chemoreceptor activity. Subsequently, although the afferent fibers were still active and could be vigorously stimulated by nicotine, they no longer responded to changes in PaO2 or to doses of cyanide, antimycin A, or FCCP. These results separate stimulation of chemoreceptor afferents by hypoxia and metabolic inhibitors and uncouplers from that by nicotine and suggest that intact oxidative phosphorylation, required for maintenance of the intracellular high-energy phosphate levels, forms the basis of O2 chemoreception in the carotid body.
A quantitative comparison of the responses between aortic and carotid chemoreceptors to steady-state levels of arterial CO2 and O2 partial pressure was made in 35 cats anesthetized, paralyzed, and artificially ventilated. The measurements on the two receptors were made simultaneously in 6 cats and separately in 29 cats. The response of aortic chemoreceptors to a CO2 stimulus was a fraction of that of carotid chemoreceptors, and the response to hypoxia was relatively blunted. The differences between the two chemoreceptors are quantitative rather than qualitative. Since a low arterial CO2 partial pressure stimulus is known to attenuate the hypoxic response of carotid chemoreceptors, it is suggested that the low CO2 response of aortic body chemoreceptors is responsible for their blunted hypoxic response.
The effects of normobaric hyperoxia on carotid body chemosensory function in the cat were studied. The hypothesis was that carotid body chemosensory function would be affected by chronic exposure to 100% O2 at sea level. It was based on the assumptions that carotid body tissue is exposed to high PO2 because of its high blood flow and that its O2 chemosensing mechanism is sensitive to O2 radical-induced reactions. Twelve cats were exposed to 100% O2 for 60-67 h, and 10 control cats were maintained in room air at sea level. They were anesthetized with pentobarbital sodium (Nembutal), and chemosensory afferents from a cut carotid sinus nerve were isolated and identified. The responses of single or a few clearly identifiable chemoreceptor afferents to isocapnic hypoxia and hypercapnia during hyperoxia and to the bolus injections of cyanide, nicotine, and dopamine were studied. We found that chronic hyperoxia severely blunted or eliminated the O2-sensitive response of the carotid chemoreceptors while augmenting the hypercapnic response. The response to cyanide but not to nicotine and dopamine were attenuated. Thus the hypoxic and hypercapnic responses that normally interact were separable. The lack of the cyanide response was consistent with the lack of the hypoxic response, suggesting a possible shared mechanism of carotid chemoreceptor response. Qualitatively normal responses to dopamine and nicotine indicated that the respective receptors were relatively intact after chronic exposure to hyperoxia and that the sensory nerves themselves were not affected by the prolonged O2 exposure.
The effects of carbon monoxide inhalation and of consequent carboxyhemoglobinemia (HbCO) on the discharge rates of aortic body and carotid body chemoreceptor afferents were investigated in 18 anesthetized cats. In 10 experiments both aortic and carotid chemoreceptor activities were monitored simultaneously. Carbon monoxide inhalation during normoxia always stimulated aortic chemoreceptors before carotid chemoreceptors, and the steady-state response of aortic chemoreceptors to HbCO was greater than that of most carotid chemoreceptors. Only 2 of the 18 carotid chemoreceptor fibers tested showed a distinct increase in activity in response to moderate increases in HbCO%. Thus, oxyhemoglobin contributed substantially to maintain tissue PO2 of all aortic chemoreceptors and of a few carotid chemoreceptors. Hyperoxia diminished the response of both aortic and carotid chemoreceptors to HbCO, indicating a lowered tissue PO2 as the stimulus source. We hypothesize that the aortic bodies have a much lower perfusion relative to their O2 utilization compared to the carotid bodies. As a consequence, the aortic chemoreceptors are able to act as a sensitive monitor of O2 delivery and to generate a circulatory chemoreflex for O2 homeostasis. carotid chemoreceptors monitor O2 tension and initiate strong reflex effects on the level of ventilation.
Effects of dopamine and of a dopaminergic blocker, haloperidol, on the responses of carotid body chemoreceptors to hypoxia and hypercapnia were investigated in 16 anesthetized cats. Intravenous infusion of dopamine (10-20 micrograms.min-1) decreased carotid body chemoreceptor responses to hypoxia and hypercapnia. The effect was greater at higher levels of arterial oxygen and carbon dioxide tension (PaO2 and PaCO2) stimulus. Thus, the magnitude of the dopamine effect depended on the degree of both PO2- and PCO2-mediated excitation of the receptors. Haloperidol potentiated responses to both hypoxia and hypercapnia but apparently did not stimulate the receptors in the absence of these stimuli. Potentiation by haloperidol and inhibition by dopamine of excitatory effects due to PaO2 decrease and PaCO2 increase are complementary. The data suggest that chemoreception of dopamine, O2, and CO2 converge at some site in the carotid body. Persistence of hypoxic and hypercapnic responses, following dopamine-blocking doses of haloperidol, does not support the theory that regulation of dopamine release is responsible for O2 and CO2 chemoreception in carotid body of the cat.
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