Arterial chemoreceptor involvement in salicylate‐induced hyperventilation in rats

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 (200mgkg-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 (10min) increase in respiration occurred regardless of whether or not the carotid nerves were sectioned. 3 Intravenous infusions of sodium salicylate (0.5 or 4mgkg-'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 crossperfusion 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 salicylateinduced 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.

Chemical Mediators of the Muscle Ergoreflex in Chronic Heart Failure

“…28,29 These pharmacological properties could have a confounding effect on the observed findings. Specifically designed studies are required to confirm the role of prostaglandins on the muscle ergoreflex.…”

Potentiation by cyclooxygenase inhibitors of the release of catecholamines from the rabbit carotid body and its reversal by prostaglandin E2

“…Regarding the mechanism of action of salicylates on the production ofhyperventilation, it will appear that the rapid hyperventilation observed immediately (within 1 min) after a high dose of the drug [6] could in fact be due to an uncoupling effect, but the long lasting hyperreactivity to hypoxia [10] can be adequately explained on the basis of our findings. Thus, an inhibition of prostaglandin synthesis will, on the arrival of a hypoxic stimulus, lead to an exaggerated release of catecholamines (and probably of other neurotransmitters) and a concurrent exaggerated activity in the carotid sinus nerve and ventilatory response.…”

“…Salicylates at high doses stimulate ventilation, the effect being mediated by peripheral and central chemoreceptors [6], It has been reported also that salicylates potentiate the carotid body-mediated hyperventilation produced by hypoxia in man [10]. The mechanism of action of salicylates at the carotid body (CB) level has been related to their well known respiratory uncoupling effect [3, 61. On the other hand, it is well known also that salicylates are potent and irreversible inhibitors of cyclooxygenase, an enzyme involved in the synthesis of prostaglandins [4].…”

In vitro activation of cyclo‐oxygenase in the rabbit carotid body: effect of its blockade on [3H]catecholamine release.

“…The hyperventilation produced by anti-inflammatory drugs at therapeutic doses is partly mediated by their action on the CB, and it was previously proposed that they might activate the CB chemoreceptors as a result of their non-specific uncoupling actions (McQueen et al 1989). The present study, however, indicates that anti-inflammatory agents may activate chemoreceptor cells by their specific ability to inhibit cyclo-oxygenase.…”

“…In addition, Riley, Legawiec, Santiago & Edelman (1977) showed that high therapeutic doses of aspirin in humans induced hyperventilation and potentiated the hypoxic ventilatory response. A direct participation of the CB in mediating this ventilatory response to aspirin was demonstrated by McQueen, Ritchie & Birrell (1989) by showing that ASA increased CSN discharge in the rat. These authors suggested that the effect of ASA on the CB was due to its known action as an uncoupler of oxidative phosphorylation.…”