Airway microvascular permeability during allergic responses

Microvascular leakage at postcapillary venules of the bronchial circulation is caused by inflammatory cell-derived mediators and substance P. Modulation of this leakage appears to be important for asthma therapy. In this presentation, we will report the inhibitory effect of some agents on neurogenic as well as allergen-induced airway microvascular hyperpermeability in the immediate and late phase in ovalbumin (OA)-sensitized guinea-pigs. OA inhalation caused immediate airway microvascular leakage, as assessed by Evans blue dye extravasation. The ATP-sensitive potassium channel opener BRL 38227 significantly inhibited the leakage. BRL 38227 also inhibited exogenous histamine- and leukotriene-induced extravasation, but had no effect on OA- induced histamine release from minced lung tissues. These results suggest that the ATP-sensitive potassium channel opener inhibits the allergic airway microvascular leakage, possibly because of its effect on the postcapillary venules. Monastral blue dye is useful for detecting the site of vascular leakage because the dye is trapped within the endothelium. Using this technique, we examined the effect of a bradykinin 2 (B₂) antagonist, an NK₁ receptor antagonist, and a nitric oxide synthase (NOS) inhibitor on the extravasation in the late-phase airway response. Airway eosinophil accumulation and vascular permeability were observed 3.5 to 6 hrs after the OA inhalation. B₂ antagonist, NK₁ antagonist, and NOS inhibitor significantly inhibited the vascular extravasation. From the above results, we conclude that the ATP-sensitive potassium channel opener, B₂- and NK₁- receptor antagonists, and NOS inhibitor may have therapeutic potential for allergic airway inflammation.