Capsazepine abolishes pulmonary chemoreflexes induced by capsaicin in anesthetized rats

Capsaicin stimulates vagal pulmonary C-fiber afferents and elicits pulmonary chemoreflex, characterized by apnea, bradycardia, and hypotension. Similar reflex responses can be also evoked by phenylbiguanide (PBG), another potent and commonly used stimulant of these afferents. This study was carried out to determine the effect of capsazepine, a competitive antagonist of capsaicin, on the reflex responses and C-fiber afferent activity evoked by capsaicin and PBG in anesthetized rats. Intravenous infusion of capsazepine did not cause any significant change in the baseline breathing pattern, but it completely abolished the pulmonary chemoreflex elicited by bolus injection of capsaicin (1-2 μg/kg iv) and its blocking effect was rapidly reversible. In contrast, the reflex responses to PBG (1-4 μg/kg iv) were not altered by capsazepine despite the fact that they could be effectively prevented by the desensitization of C-fiber afferents resulting from a prior capsaicin treatment. Indeed, although both capsaicin and PBG evoked an abrupt and intense burst of discharge from the vagal C-fiber afferent endings in the lungs, the stimulatory effect of the former, but not the latter, was abolished in the same fibers by capsazepine. In summary, capsazepine selectively blocks the stimulatory effect of capsaicin on the vagal C-fiber afferents in the lungs and the consequent pulmonary chemoreflex, presumably by blocking the putative 'capsaicin receptors' located in the membrane of these afferent endings.