Abstract

The relative activities of three bronchoconstrictive mediators of anaphylaxis, prostaglandin (PG) D2, PGF2 alpha and histamine, were investigated in anesthetized dogs using two different measures of peripheral lung reactivity: resistance to flow through collateral airways (Rcoll) and dynamic lung compliance (Cdyn). In the collateral system, the three agonists exhibited approximately 3-fold differences in their relative activities when administered by rapid injection into the superior vena cava, with PGD2 greater than PGF2 alpha greater than histamine. PGD2 was approximately three times more active than PGF2 alpha in reducing Cdyn, whereas responses to PGF2 alpha and histamine were equivalent. These relationships were unchanged in vagotomized animals. Pretreatment with atropine (1 mg/kg) significantly attenuated changes in Rcoll, but had only small and inconsistent effects on changes in Cdyn. Although the time to initial response in both measures of peripheral airways reactivity was similar, the time to maximal response in Rcoll was approximately twice that of Cdyn. In lung parenchymal strips, the rank order of contractile activity of the three mediators was opposite that observed in the peripheral airways in vivo. These data demonstrate that airflow through the collateral system can be modulated by mediators of anaphylaxis in the pulmonary circulation and suggest that such mediators may influence ventilation/perfusion relationships in the lung periphery through their differential effects on peripheral airways and other parenchymal contractile elements. The present study also indicates that the determinants of flow through the collateral system exhibit certain basic pharmacologic and physiologic differences from those of Cdyn and suggests that these two measures of peripheral airways reactivity are not equivalent.