Pulmonary chemoreflex sensitivity is enhanced by prostaglandin E₂ in anesthetized rats

Stimulation of vagal pulmonary C-fiber afferents by chemical irritants is believed to be responsible for eliciting the pulmonary chemoreflex (apnea, bradycardia, and hypotension). This study was carried out in anesthetized Sprague-Dawley rats to determine whether the pulmonary chemoreflex was altered by prostaglandin E₂ (PGE₂), which is one of the major inflammatory mediators in the lungs and is known to enhance the sensitivity of C-fiber afferents in several other organ systems. Capsaicin injected at a dose just above the stimulation threshold (0.25 or 0.5 μg/kg iv) elicited a very mild respiratory and cardiovascular depression. In sharp contrast, during a constant infusion of PGE₂ (1.5 μg · kg^-1 · min^-1 iv), the same dose of capsaicin triggered a long apnea, with the expiratory duration reaching 843% of the baseline expiratory duration, accompanied by intense bradycardia and hypotension. Similarly, the pulmonary chemoreflex response elicited by a bolus injection of phenyl biguanide (1 or 2 μg/kg iv) was also greatly augmented by PGE₂. These enhanced responses were completely abolished by a perineural capsaicin treatment of both cervical vagi to selectively block the conduction of C fibers, suggesting the involvement of these afferents. Electrophysiological recording of pulmonary C-fiber afferent activity further supported our conclusion that the sensitivity of these sensory endings to capsaicin challenge was potentiated by PGE₂.