Neurogenic airway microvascular leakage induced by toluene inhalation in rats
2012
Sakamoto, Tatsuo | Kamijima, Michihiro | Miyake, Mio
Toluene is a representative airborne occupational and domestic pollutant that causes eye and respiratory tract irritation. We investigated whether a single inhalation of toluene elicits microvascular leakage in the rat airway. We also evaluated the effects of CP-99,994, a tachykinin NK₁ receptor antagonist, and ketotifen, a histamine H1 receptor antagonist with mast cell-stabilizing properties, on the airway response. The content of Evans blue dye that extravasated into the tissues was measured as an index of plasma leakage. Toluene (18–450ppm, 10min) concentration-dependently induced dye leakage into the trachea and main bronchi of anesthetized and mechanically ventilated rats. Toluene at concentrations of ≥50 and ≥30ppm caused significant responses in the trachea and main bronchi, respectively, which both peaked after exposure to 135ppm toluene for 10min. This response was abolished by CP-99,994 (5mg/kg i.v.), but not by ketotifen (1mg/kg i.v.). Nebulized phosphoramidon (1mM, 1min), a neutral endopeptidase 24.11 inhibitor, significantly enhanced the response induced by toluene (135ppm, 10min) compared with nebulized 0.9% saline (1min). These results show that toluene can rapidly increase airway plasma leakage that is predominantly mediated by tachykinins endogenously released from airway sensory nerves. However, mast cell activation might not be important in this airway response.
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