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

Am J Physiol Lung Cell Mol Physiol. 2008 Jul;295(1):L214-9. doi: 10.1152/ajplung.00498.2007. Epub 2008 May 16.


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(pl)) time-response curve, were measured, and histamine PC(100) (provocation concentration causing a 100% increase of P(pl)) 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(pl), 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 (<90 min). In addition, Y-27632 reduced the number of total inflammatory cells, eosinophils, macrophages, and neutrophils recovered from the BAL. Altogether, inhaled Y-27632 protects against acute allergen-induced bronchoconstriction, development of AHR after the EAR and LAR, and airway inflammation in an established guinea pig model of allergic asthma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Allergens / toxicity*
  • Amides / pharmacology*
  • Animals
  • Asthma / chemically induced
  • Asthma / enzymology
  • Asthma / pathology
  • Asthma / prevention & control*
  • Disease Models, Animal
  • Enzyme Inhibitors / pharmacology*
  • Guinea Pigs
  • Inflammation / chemically induced
  • Inflammation / enzymology
  • Inflammation / prevention & control
  • Male
  • Neutrophils / enzymology*
  • Neutrophils / pathology
  • Pyridines / pharmacology*
  • Time Factors
  • rho-Associated Kinases / antagonists & inhibitors*
  • rho-Associated Kinases / metabolism


  • Allergens
  • Amides
  • Enzyme Inhibitors
  • Pyridines
  • Y 27632
  • rho-Associated Kinases