Role of pulmonary C fibers in adenosine-induced respiratory inhibition in anesthetized rats

Abstract

The clinical use of adenosine is commonly associated with pulmonary side effects, namely dyspnea, that suggest the possible involvement of bronchopulmonary sensory afferents. Our objective in this study was to characterize the effects of adenosine on breathing and to determine whether the vagal pulmonary afferents play a role in mediating these effects. We measured respiratory and cardiovascular changes in anesthetized, spontaneously breathing rats after bolus injections of adenosine at therapeutic doses. Right atrial injection of adenosine (0.04-0.6 mg/kg) elicits, in a dose-dependent manner, a pulmonary chemoreflex-like response consisting of a delayed apnea, bradycardia, and hypotension. In contrast, the classic capsaicin-elicited pulmonary chemoreflex occurs immediately after injection. Perineural capsaicin treatment of the cervical vagi blocked the adenosine-induced respiratory inhibition. Left ventricular administration of adenosine failed to elicit an apneic response. Pretreatment with the adenosine A1-receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine attenuated the adenosine-induced apnea. These results indicate that adenosine elicits a respiratory inhibition via stimulation of pulmonary C fibers and that activation of the A1-receptor is probably involved. It is unclear, however, what accounts for the exceedingly long latency in this response.

Activation of pulmonary C fibres by adenosine in anaesthetized rats: role of adenosine A1 receptors

“…The effective blockade of rat Aµ receptors in vivo by DMPX has already been demonstrated in our recent study: DMPX at this dose inhibited the hypotension induced by DPMA, an Aµ receptor agonist (Kwong et al 1998). It is noteworthy that DPMA does not induce apnoea in rats (Kwong et al 1998); this fact further rules out the role of Aµ receptors in Ado-induced C fibre stimulation. The time courses of C fibre stimulation by Ado and capsaicin are distinctly different.…”

“…Patients receiving Ado for diagnostic or therapeutic purposes frequently experience dyspnoea and chest discomfort of more than moderate severity (Rankin et al 1992). The stimulation of pulmonary C fibres reported in this study and the consequent apnoea (Kwong et al 1998) strongly suggest a role of these nerve endings in causing these adverse effects. However, other mechanisms should also be considered.…”

“…Contrary to this expectation, the left-ventricular injection of Ado, which failed to activate pulmonary C fibres, caused the same degree of cardiovascular response as that after right-atrial injection (Figs 2 and 3). Furthermore, the cardiovascular response to Ado was not significantly attenuated either by selective blockade of C fibre conduction (Kwong et al 1998) or by bilateral vagotomy (Fig. 4).…”

“…an Aµ receptor agonist (Kwong et al 1998). In all five study series, at least 10 min elapsed between injections of Ado or capsaicin.…”

Adenosinergic and cholinergic control mechanisms during hypoxia in the epaulette shark (Hemiscyllium ocellatum), with emphasis on branchial circulation

“…An increase in ventilation frequency as a response to hypoxia is widespread among fishes but, to our knowledge, this is the first indication of an involvement of adenosine in a respiratory reflex in fish. In rat, injection of adenosine into the circulation inhibits respiration through vagal pulmonary C fibres (Kwong et al, 1998). As adenosine levels are likely to increase during hypoxia, a role of adenosine in ventilatory control in fish during hypoxia needs further attention.…”