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 microgram/kg i.v.) elicited a very mild respiratory and cardiovascular depression. In sharp contrast, during a constant infusion of PGE2 (1.5 micrograms.kg-1.min-1 i.v.), 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 micrograms/kg i.v.) 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.
Lee
L Y
LY
Department of Physiology, University of Kentucky, Lexington 40536-0084, USA.
Morton
R F
RF
D000704:Analysis of Variance; D000818:Animals; D001645:Biguanides / Q000494:pharmacology; D002211:Capsaicin / Q000494:pharmacology; D002628:Chemoreceptor Cells / Q000187:drug effects* / Q000502:physiology; D015232:Dinoprostone / Q000494:pharmacology*; D005260:Female; D007004:Hypoglycemic Agents / Q000494:pharmacology; D008168:Lung / Q000187:drug effects / Q000294:innervation* / Q000502:physiology; D008297:Male; D009412:Nerve Fibers / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014630:Vagus Nerve / Q000187:drug effects*
D001645:Biguanides; D007004:Hypoglycemic Agents; D015232:Dinoprostone; D002211:Capsaicin; C008846:phenyl biguanide