Histamine and leukotrienes mediate pulmonary hypersensitivity to antigen in guinea pigs.

Abstract

To study roles of histamine and slow-reacting substance of anaphylasis (SRS-A) in mediating airway responses following antigen challenge, mediator antagonists were administered to guinea pigs sensitized with ovalbumin 10 days before the study. Twenty-three animals were divided into the following five treatment groups: 1) saline only (control 1, n = 5); 2) antigen challenged (n = 5); 3) antigen + methapyrilene (antihistamine, n = 5); 4) FPL 55712 only (SRS-A antagonist, control 2; n = 4), and 5) antigen + FPL 55712 (n = 4). Control groups were not sensitized. Experimental values were compared with those of control 1 at equal times after injections. Pulmonary resistance (RL), dynamic compliance (Cdyn), breathing frequency (f), tidal volume, minute ventilation (VE) and systemic arterial pressure were measured for 15-20 min just before (base line) and for up to 30 min after saline or antigen administration. Antigen challenge alone induced maximal respiratory changes at 5 min. RL increased 131 +/- 28% above base line (P less than 0.05), whereas Cdyn decreased slightly (28 +/- 10%, P less than 0.05). Antihistamine almost eliminated all changes in RL but did not affect decreased Cdyn. On the other hand, FPL 55712 eliminated changes in both RL and Cdyn. Both antagonists blocked the transient increase in VE, but neither blocked the rise in f at 5 min. We conclude that antigen-induced bronchoconstriction (RL) may be primarily mediated by histamine, whereas simultaneous alterations in Cdyn may depend mainly on leukotrienes and those in f depend on neither.