Role of tachykinins in ozone-induced acute lung injury in guinea pigs.
To examine the hypothesis that the acute reversible changes caused by ozone (O3) exposure are mediated by tachykinin release, guinea pigs were depleted of tachykinins by use of repeated capsaicin (CAP) injections before O3 exposure in an attempt to prevent O3-induced functional changes. Unexpectedly, CAP pretreatment caused divergent results in the functional responses to O3. Ventilatory measurements obtained from CAP-pretreated O3-exposed (CAP-O3) animals were exacerbated rather than diminished compared with the effects of O3 alone. Similarly, lavage fluid protein accumulation was enhanced in the CAP-O3 group compared with the O3-exposed group. In better agreement with our initial hypothesis, the CAP-O3 group was less responsive than the O3-exposed animals to histamine aerosol challenge. Additionally, Evans blue dye accumulation, a hallmark of tachykinin release, was increased in O3-exposed animals and was partially blocked in the CAP-O3 group. These data suggest that tachykinin-containing sensory fibers are unlikely to mediate the acute effects of O3 exposure on tidal breathing and lavage fluid protein accumulation but may play a role in causing post-O3 airway hyperreactivity and protein extravasation into the trachea.
Tepper
J S
JS
ManTech Environmental Technology, Inc., Research Triangle Park 27709.
Costa
D L
DL
Fitzgerald
S
S
Doerfler
D L
DL
Bromberg
P A
PA
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D002199:Capillary Permeability; D002211:Capsaicin / Q000494:pharmacology; D006168:Guinea Pigs; D008170:Lung Compliance; D008171:Lung Diseases / Q000139:chemically induced*; D008297:Male; D010126:Ozone; D011506:Proteins / Q000032:analysis; D012119:Respiration; D015320:Tachykinins / Q000037:antagonists & inhibitors / Q000502:physiology*; D014132:Trachea / Q000098:blood supply
D011506:Proteins; D015320:Tachykinins; D010126:Ozone; D002211:Capsaicin