The inhaled Rho kinase inhibitor Y-27632 protects against allergen-induced acute bronchoconstriction, airway hyperresponsiveness, and inflammation

Dedmer Schaafsma*, I. Sophie T. Bos, Annet B. Zuidhof, Johan Zaagsma, Herman Meurs

*Bijbehorende auteur voor dit werk

OnderzoeksoutputAcademicpeer review

49 Citaten (Scopus)

Samenvatting

Recently, we have shown that allergen-induced airway hyperresponsiveness (AHR) after the early (EAR) and late (LAR) asthmatic reaction in guinea pigs could be reversed acutely by inhalation of the Rho kinase inhibitor Y-27632. The present study addresses the effects of pretreatment with inhaled Y-27632 on the severity of the allergen-induced EAR and LAR, the development of AHR after these reactions, and airway inflammation. Using permanently instrumented and unrestrained ovalbumin (OA)-sensitized guinea pigs, single OA challenge-induced EAR and LAR, expressed as area under the lung function (pleural pressure, P(p1)) time-response curve, were measured, and histamine PC(100) (provocation concentration causing a 100% increase of P(p1)) values were assessed 24 h before, and at 6 and 24 h after, the OA challenge (after the EAR and LAR, respectively). Thirty minutes before and 8 h after OA challenge, saline or Y-27632 (5 mM) was nebulized. After the last PC(100) value, bronchoalveolar lavage (BAL) was performed, and the inflammatory cell profile was determined. It was demonstrated that inhalation of Y-27632 before allergen challenge markedly reduced the immediate allergen-induced peak rise in P(p1), without significantly reducing the overall EAR and LAR. Also, pretreatment with Y-27632 considerably protected against the development of AHR after the EAR and fully prevented AHR after the LAR. These effects could not be explained by a direct effect of Y-27632 on the histamine responsiveness, because of the short duration of the acute bronchoprotection of Y-27632 (

Originele taal-2English
Pagina's (van-tot)L214-L219
Aantal pagina's6
TijdschriftAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume295
Nummer van het tijdschrift1
DOI's
StatusPublished - jul-2008

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