Effects of Rho-kinase inhibition in lung tissue with chronic inflammation

• Distal lung inflammation was reduced by Rho-kinase inhibitor.
• Matrix remodeling was reduced by Rho-kinase inhibitor.
• Oxidative stress was reduced by Rho-kinase inhibitor.
• Distal lung responsiveness was reduced by Rho-kinase inhibitor.

We evaluated whether Rho-kinase inhibition (Y-27632) modulated distal lung responsiveness, inflammation, extracellular matrix remodeling and oxidative stress activation in guinea pigs (GPs) with chronic allergic inflammation. GPs were submitted to inhalation of ovalbumin (OVA-2×/week/4 weeks). From the 5th inhalation on, the Rho-kinase inhibitor group animals were submitted to Y-27632 inhalation 10 min before each inhalation of OVA. Seventy-two hours after the seventh inhalation, the oscillatory mechanics of the distal lung strips were assessed under the baseline condition and after the ovalbumin challenge. Subsequently, the lung slices were submitted to morphometry. Rho-kinase inhibition in the ovalbumin-exposed animals attenuated distal lung elastance and resistance, eosinophils, IL-2, IL-4, IL-5, IL-13, TIMP-1, MMP-9, TGF-β, IFN-γ, NF-κB and iNOS-positive cells and the volume fraction of 8-iso-PGF2α, elastic, collagen and actin in alveolar walls compared with the OVA group (P < 0.05). Rho-kinase inhibition contributed to the control of distal lung responsiveness, eosinophilic and Th1/Th2 responses and extracellular matrix remodeling in an animal model of chronic allergic inflammation.