Abstract
1. The extent to which peripheral arterial chemoreceptors are involved in the respiratory stimulant action of salicylates has been investigated in rats. 2. Injection of sodium salicylate (200 mg kg-1, single dose i.v.) caused a rapid transient hyperventilation that was not obtained when the carotid chemoreceptors were denervated by section of the carotid sinus nerves. A delayed (10 min) increase in respiration occurred regardless of whether or not the carotid nerves were sectioned. 3. Intravenous infusions of sodium salicylate (0.5 or 4 mg kg-1 min-1) caused hyperventilation in barbiturate-anaesthetized rats. The threshold dose for respiratory stimulation was significantly lower when the carotid sinus nerves were intact than when they were bilaterally sectioned, and the same pattern was observed following intravenous injections of sodium salicylate (cumulative doses) in anaesthetized and conscious rats. 4. Bilateral sectioning of the vagosympathetic nerve trunks did not significantly affect hyperventilation evoked by salicylate, suggesting that this response does not involve actions of salicylate on sensory receptors innervated by these nerves. 5. Administration of salicylate close-arterial to a carotid body, by local perfusion or cross-perfusion of a carotid sinus, led to an increase in respiration when the ipsilateral carotid nerve was intact, but not when it was sectioned. 6. Neuropharmacological studies on anaesthetized rats showed that chemosensory discharge, recorded from a sectioned carotid nerve, increased in response to salicylate injections with a similar dose-response pattern to the hyperventilation. Salicylate had no effect on baroreceptor discharge. 7. We conclude from our experiments that arterial chemoreceptors do contribute to salicylate-induced hyperventilation, and are almost exclusively responsible for the initial phase of the response in rats. Later increases in breathing are independent of reflexes from arterial chemoreceptors and result from actions at other sites, including the CNS. The therapeutic implications of our results are discussed.