Significance of Thromboxane A₂ in Naoci-Induced Airway Hyperresponsiveness in Guinea Pigs

Abstract

To examine whether thromboxane A₂ (TXA₂) is involved in mechanisms causing NaOCI-induced airway hyperresponsiveness in guinea pigs, we investigated the effects of a thromboxane synthase inhibitor, OKY-046 (sodium (E)-3-[4-(1-imidazolymethyl) phenyl]-2-propionate), on NaOCI-induced airway hyperresponsiveness together with airway permeability and morphologic features. The effect of OKY-046 (100 mg/kg, ip) on NaOCI-induced airway hyperresponsiveness was assessed by changes in specific airway resistance (SRaw in cm H₂O · s) to inhaled histamine aerosol in unanesthetized, spontaneously breathing guinea pigs. OKY-046 pretreatment suppressed NaOCI-induced airway hyperresponsiveness, whereas OKY-046 per se did not affect the airway responsiveness. Airway permeability was assessed by quantifying extravascular Evans blue dye into the trachea after intravenous injection. Evans blue dye content was significantly greater in the OKY-046-pretreated NaOCI inhalation group. This fact indicates that airway permeability was increased by NaOCI inhalation associated with OKY-046 pretreatment. Neither NaOCI inhalation nor OKY-046 pretreatment alone caused increased airway permeability. The effect of OKY-046 on histopathological findings was equivocal. There were no significant differences in the number of polymorphonuclear leukocytes and eosinophils in both epithelium and the lamina propria among the study groups. Our study indicates that TXA₂ may be an important mediator of NaOCI-induced airway hyperresponsiveness.