The relative activities of three bronchoconstrictive mediators of anaphylaxis, prostaglandin (PG) D2, PGF(2α), and histamine, were investigated in anesthetized dogs using two different measures of peripheral lung reactivity: resistance to flow through collateral airways (R(coll)) and dynamic lung compliance (C(dyn)). In the collateral system, the three agonists exhibit approximately 3-fold differences in their relative activities when administered by rapid injection into the superior vena cava, with PGD2 > PGF (2α) histamine. PGD2 was approximately three times more active than PGF(2α) in reducing C(dyn), whereas responses to PGF(2α) and histamine were equivalent. These relationships were unchanged in vagotomized animals. Pretreatment with atropine (1 mg/kg) significantly attenuated changes in R(coll), but had only small and inconsistent effects on changes in C(dyn). Although the time to initial response in both measures of peripheral airways reactivity was similar, the time to maximal response in R(coll) was approximately twice that of C(dyn). 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 C(dyn) and suggests that these two measures of peripheral airways reactivity are not equivalent.
|Original language||English (US)|
|Number of pages||7|
|Journal||Journal of Pharmacology and Experimental Therapeutics|
|State||Published - Jan 1 1985|
ASJC Scopus subject areas
- Molecular Medicine