ANTIGEN-INDUCED CONTRACTION OF GUINEA-PIG ISOLATED PULMONARY-ARTERIESAND LUNG PARENCHYMA

We characterized the kinetics of and determined the mediators involved in antigen-induced contraction of pulmonary arteries (PA) and lung pa renchyma isolated from actively sensitized guinea pigs. Ovalbumin (10( -2) mg/ml) induced contractions of PA rings, which reached maximum amp litude bv 2 min and decayed to 50% of maximum by 4-6 min. Pyrilamine ( 10(-6) M) delayed the onset of contraction and decreased the peak of t he response bv >50%. Metiamide (10(-4) M) partially reversed this effe ct. The addition of indomethacin (10(-6) M) to the combination of pyri lamine and metiamide had no significant effect. The further addition o f the leukotriene (LT) D4/LTE4 receptor antagonist SKF 104353 (10(-5) M) reduced the contraction by >80%. The maximum amplitude of antigen-i nduced contraction of parenchymal strips was reached by 15 min and was sustained for >60 min. In these tissues, SKF 104353 inhibited the con traction by approximately 35%, but the histamine receptor antagonists and indomethacin had no significant effect. These results suggest that both histamine and sulfidopeptide LTs mediate antigen induced contrac tion of PA, whereas sulfidopeptide LTs, but not histamine, are involve d in the parenchymal response.