Effect of cromolyn on adenosine-induced airway microvascular leakage in sensitized rats

Inhalation of adenosine causes bronchoconstriction in asthmatic subjects, b ut the effect of this purine nucleotide on airway vascular permeability is unknown. In order to determine whether adenosine produces airway microvascular leaka ge and, if so, to examine the effect of cromolyn (sodium cromoglycate (SCG) ) on this extravasation of Evans blue was measured in the airways of ovalbu min-sensitized Brown Norway rats. Inhaled adenosine caused microvascular leakage in sensitized but not in non sensitized rats, and the response was abolished by capsaicin pretreatment o r the tachykinin neurokinin-1 receptor antagonist FK888, Adenosine-induced vascular leakage became apparent in nonsensitized rats when treated with ph osphoramidon, and airway neutral endopeptidase activity was lower in sensit ized than in nonsensitized animals. The extravasation induced by adenosine in sensitized rats was dose dependently inhibited by SCG aerosols. SCG like wise inhibited microvascular responses to substance P, but had no effect on those to platelet-activating factor. These results suggest that: 1) adenosine induces airway microvascular leaka ge in sensitized rats through stimulation of neurokinin-l receptors; 2) thi s effect is associated with a sensitization-induced decrease in neutral end opeptidase activity; and 3) sodium cromoglycate inhibits adenosine-induced extravasation, presumably rin functional antagonism of tachykinins.