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This Article Full Text Free Full Text (PDF) Free All Versions of this Article: 99/6/2080    most recent 00537.2005v1 Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Web of Science (1) Citing Articles via Google Scholar Google Scholar Articles by Van Scott, M. R. Articles by Stallings, H. W. Search for Related Content PubMed PubMed Citation Articles by Van Scott, M. R. Articles by Stallings, H. W., III

Separation of bronchoconstriction from increased ventilatory drive in a nonhuman primate model of chronic allergic asthma

Departments of ¹Physiology and ²Comparative Medicine, East Carolina University, Greenville, North Carolina

Submitted 6 May 2005 ; accepted in final form 11 August 2005

The relationship between allergen-induced ventilatory drive and bronchoconstriction was investigated in dust mite-sensitive cynomolgus macaques periodically exposed to low doses of aerosolized antigen for up to 5.5 yr. Initially, the animals responded to aerosolized dust mite allergen at a concentration of 350 arbitrary units (AU)/ml with simultaneous increases in lung resistance (RL) and respiratory rate (RR). With time, RL and RR became differentially sensitive to allergen provocation. At the end of the study period, aerosolized allergen at a concentration of 15 AU/ml doubled RR without increasing RL. When mechanically ventilated to maintain tidal volume, higher concentrations of allergen could be delivered, and RL increased. Inhaled disodium cromoglycate and intravenous diphenhydramine attenuated the increase in RR, indicating that allergen-induced release of histamine and activation of H₁ receptors mediated the response. Inhaled -adrenergic agonists attenuated the RR response to dust mite and to direct histamine provocation. These results demonstrate that chronic periodic allergen challenge increases the allergic sensitivity of histamine-dependent reflexes controlling ventilatory drive. Activation of these reflexes is independent of overt bronchoconstriction, but can be inhibited by -adrenergic agonists, indicating that -adrenergic agonists exert their effect independent of bronchodilation.

C-fiber endings; rapidly adapting receptors; histamine; -adrenergic agonist