Potentiation of pulmonary reflex response to capsaicin 24h following whole-body acrolein exposure is mediated by TRPV1.
Pulmonary C-fibers are stimulated by irritant air pollutants producing apnea, bronchospasm, and decrease in HR. Chemoreflex responses resulting from C-fiber activation are sometimes mediated by TRPV1 and release of substance P. While acrolein has been shown to stimulate C-fibers, the persistence of acrolein effects and the role of C-fibers in these responses are unknown. These experiments were designed to determine the effects of whole-body acrolein exposure and pulmonary chemoreflex response post-acrolein. Rats were exposed to either air or 3 ppm acrolein for 3 h while ventilatory function and HR were measured; 1-day later response to capsaicin challenge was measured in anesthetized rats. Rats experienced apnea and decrease in HR upon exposure to acrolein, which was not affected by either TRPV1 antagonist or NK(1)R antagonist pretreatment. Twenty-four hours later, capsaicin caused apnea and bronchoconstriction in control rats, which was potentiated in rats exposed to acrolein. Pretreatment with TRPV1 antagonist or NK(1)R antagonist prevented potentiation of apneic response and bronchoconstriction 24h post-exposure. These data suggest that although potentiation of pulmonary chemoreflex response 24h post-acrolein is mediated by TRPV1 and release of substance P, cardiopulmonary inhibition during whole-body acrolein exposure is mediated through other mechanisms.
Hazari
Mehdi S
MS
Curriculum in Toxicology, University of North Carolina, Chapel Hill, NC 27599-7270, United States. hazari.mehdi@epa.gov
Rowan
William H
WH
Winsett
Darrell W
DW
Ledbetter
Allen D
AD
Haykal-Coates
Najwa
N
Watkinson
William P
WP
Costa
Daniel L
DL
D000171:Acrolein / Q000494:pharmacology*; D000393:Air Pollutants / Q000494:pharmacology; D000818:Animals; D002211:Capsaicin / Q000008:administration & dosage / Q000494:pharmacology*; D002628:Chemoreceptor Cells / Q000187:drug effects* / Q000502:physiology; D004357:Drug Synergism; D007509:Irritants / Q000494:pharmacology*; D008297:Male; D036421:Nerve Fibers, Unmyelinated / Q000187:drug effects / Q000378:metabolism; D012123:Pulmonary Ventilation / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018040:Receptors, Neurokinin-1 / Q000187:drug effects / Q000378:metabolism; D012018:Reflex / Q000187:drug effects / Q000502:physiology; D012119:Respiration / Q000187:drug effects; D015656:Respiratory Mechanics / Q000187:drug effects / Q000502:physiology; D012137:Respiratory System / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D018689:Sensory System Agents / Q000008:administration & dosage / Q000494:pharmacology; D013373:Substance P / Q000378:metabolism; D050916:TRPV Cation Channels / Q000378:metabolism*
D000393:Air Pollutants; D007509:Irritants; D018040:Receptors, Neurokinin-1; D018689:Sensory System Agents; D050916:TRPV Cation Channels; C494484:TRPV1 receptor; D013373:Substance P; D000171:Acrolein; D002211:Capsaicin