Impaired sensorineural function after allergen-induced mediator release.
We tested the hypothesis that allergen-induced mediator release augments the magnitude of isocapnic dry gas hyperpnea-induced bronchoconstriction in sensitized guinea pigs. Male Hartley guinea pigs were sensitized by spontaneous inhalation of ovalbumin (OA) aerosol on days 0 and 7 of the study. On day 14, sensitized animals again breathed OA aerosol and were prospectively divided into a group that exhibited labored breathing (LB), presumably reflecting OA-induced inflammatory mediator release, and a group that did not exhibit LB at this time. Control guinea pigs breathed saline aerosol on days 0, 7, and 14. Bronchoalveolar lavage on day 17 disclosed relative eosinophilia in OA+LB, but not in OA-LB, animals. On day 17, the bronchoconstrictor responses to increasing intravenous (i.v.) doses of acetylcholine (ACh), substance P (SP), neurokinin A (NKA), and capsaicin, as well as dry gas hyperpnea, were measured in vivo in animals from each group. Control and OA-LB guinea pigs exhibited similar responses, but OA+LB animals demonstrated augmented bronchoconstriction induced by i.v. administration of ACh, SP, or NKA. However, despite their augmented responsiveness to these exogenous constrictor agonists, OA+LB animals displayed no greater bronchoconstriction after dry gas hyperpnea or i.v. capsaicin administration. It is known that both dry gas hyperpnea and i.v. capsaicin cause bronchoconstriction in guinea pigs by releasing endogenous tachykinins from airway sensory C-fibers. Thus, our results suggest that allergen-induced mediator release impairs endogenous tachykinin release from airway sensory C-fibers in guinea pigs.
Hsiue
T R
TR
Department of Medicine, University of Chicago, IL 60637.
Leff
A R
AR
Garland
A
A
Hershenson
M B
MB
Ray
D W
DW
Solway
J
J
D000109:Acetylcholine / Q000008:administration & dosage / Q000494:pharmacology; D000403:Airway Resistance / Q000187:drug effects / Q000502:physiology; D000485:Allergens / Q000009:adverse effects*; D000818:Animals; D016535:Bronchial Hyperreactivity / Q000503:physiopathology*; D001992:Bronchoalveolar Lavage Fluid / Q000473:pathology; D016084:Bronchoconstriction / Q000187:drug effects / Q000502:physiology*; D002211:Capsaicin / Q000008:administration & dosage / Q000494:pharmacology; D002245:Carbon Dioxide / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D004804:Eosinophils / Q000473:pathology; D006168:Guinea Pigs; D008297:Male; D015288:Neurokinin A / Q000008:administration & dosage / Q000494:pharmacology; D018377:Neurotransmitter Agents / Q000494:pharmacology*; D010047:Ovalbumin; D012120:Respiration Disorders / Q000139:chemically induced / Q000503:physiopathology*; D013373:Substance P / Q000008:administration & dosage / Q000494:pharmacology; D013990:Tidal Volume / Q000187:drug effects / Q000502:physiology
D000485:Allergens; D018377:Neurotransmitter Agents; D002245:Carbon Dioxide; D013373:Substance P; D015288:Neurokinin A; D010047:Ovalbumin; D000109:Acetylcholine; D002211:Capsaicin