Mechanisms of bronchoconstriction induced by anaphylaxis in sensitized guinea pigs

Abstract

Anaphylactic reaction in sensitized guinea pigs is known to induce bronchoconstriction when an adequate amount of antigen is administrated. This phenomenon has been established as a model of bronchial asthma. To evaluate the mechanism of bronchoconstriction in anaphylaxis, we analyzed the change of endobronchial pressure in sensitized guinea pigs. Guinea pigs weighing 300-600 g were actively sensitized by intracutaneously administrated ovalbumin (10 mg). Two weeks later they were anesthetized and mechanically ventilated with a volume type Harvard respirator. Antigen was administrated intravenously and monitoring of endotracheal pressure and systemic blood pressure was performed. Drugs to modify these reactions were administrated intraperitoneally 30 minutes before antigen challenge. In the control group, the endotracheal pressure showed a curve with the first peak between 0.5 and 1.5 minutes after the antigen challenge. When cyclooxygenase inhibitor (indomethacin) was administered before the antigen, the first peak was markedly suppressed. However, the histamine (H1)-receptor blocker did not suppress the first peak. On the other hand when 5-lipoxygenase inhibitor (AA-861) was administered before the antigen, the increase of intratracheal pressure was suppressed between 2 and 4 minutes after the antigen challenge. The above results may suggest that the first peak of intratracheal pressure derives from bronchoconstriction caused by prostaglandins or thromboxanes, and that the increase of intratracheal pressure at between 2 and 4 minutes derives from bronchoconstriction caused by leukotrienes.