Contribution of a cholinergic reflex mechanism to allergen-induced bronchial hyperreactivity in permanently instrumented, unrestrained guinea-pigs.
1. In conscious, permanently instrumented, unrestrained, ovalbumin-sensitized guinea-pigs the development of allergen-induced bronchial hyperreactivity to histamine- and methacholine-inhalation was investigated after the early as well as after the late asthmatic response. 2. The allergen-induced increase in bronchial reactivity to histamine was significantly higher than to methacholine. 3. The muscarinic receptor antagonist, ipratropium bromide (1.0 mM, 3 min inhalation), blocked methacholine-induced bronchoconstriction and caused a significant 1.7 fold inhibition of the histamine-induced bronchoconstriction of control animals. 4. A lower dose of ipratropium bromide (0.1 mM, 3 min inhalation) had no significant effect on histamine-induced bronchoconstriction in control animals, but significantly reduced the allergen-induced increase in bronchial reactivity to histamine between the early and late asthmatic response. At 1.0 mM ipratropium bromide, no further reduction was observed. 5. These results clearly indicate that an exaggerated cholinergic reflex mechanism contributes to allergen-induced bronchial hyperreactivity to histamine.
Santing
R E
RE
Department of Medicinal Chemistry and Molecular Pharmacology, University Centre for Pharmacy, Groningen, The Netherlands.
Pasman
Y
Y
Olymulder
C G
CG
Roffel
A F
AF
Meurs
H
H
Zaagsma
J
J
D000485:Allergens / Q000494:pharmacology*; D000818:Animals; D001249:Asthma / Q000503:physiopathology; D016535:Bronchial Hyperreactivity / Q000503:physiopathology*; D016084:Bronchoconstriction / Q000187:drug effects; D006168:Guinea Pigs; D006632:Histamine / Q000494:pharmacology; D009241:Ipratropium / Q000494:pharmacology; D008688:Methacholine Compounds / Q000037:antagonists & inhibitors / Q000494:pharmacology; D010047:Ovalbumin / Q000276:immunology; D010275:Parasympathetic Nervous System / Q000502:physiology*; D012018:Reflex / Q000502:physiology*; D012129:Respiratory Function Tests
D000485:Allergens; D008688:Methacholine Compounds; D006632:Histamine; D010047:Ovalbumin; D009241:Ipratropium