Effect of cromolyn on adenosine-induced airway microvascular leakage in sensitized rats.
Inhalation of adenosine causes bronchoconstriction in asthmatic subjects, but the effect of this purine nucleotide on airway vascular permeability is unknown. In order to determine whether adenosine produces airway microvascular leakage and, if so, to examine the effect of cromolyn (sodium cromoglycate (SCG)) on this extravasation of Evans blue was measured in the airways of ovalbumin-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 or the tachykinin neurokinin-1 receptor antagonist FK888. Adenosine-induced vascular leakage became apparent in nonsensitized rats when treated with phosphoramidon, and airway neutral endopeptidase activity was lower in sensitized than in non-sensitized animals. The extravasation induced by adenosine in sensitized rats was dose dependently inhibited by SCG aerosols, SCG likewise 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 leakage in sensitized rats through stimulation of neurokinin-1 receptors; 2) this effect is associated with a sensitization-induced decrease in neutral endopeptidase activity; and 3) sodium cromoglycate inhibits adenosine-induced extravasation, presumably via functional antagonism of tachykinins.
Tamaoki
J
J
First Dept of Medicine, Tokyo Women's Medical University School of Medicine, Japan.
Yamawaki
I
I
Taira
M
M
Nagano
Y
Y
Nakata
J
J
Nagai
A
A
D000241:Adenosine / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D018927:Anti-Asthmatic Agents / Q000494:pharmacology*; D002199:Capillary Permeability / Q000187:drug effects*; D004396:Coloring Agents; D004205:Cromolyn Sodium / Q000494:pharmacology*; D005070:Evans Blue; D005119:Extravasation of Diagnostic and Therapeutic Materials; D008297:Male; D015260:Neprilysin / Q000378:metabolism; D010047:Ovalbumin; D051381:Rats; D011914:Rats, Inbred BN; D018040:Receptors, Neurokinin-1 / Q000187:drug effects
D018927:Anti-Asthmatic Agents; D004396:Coloring Agents; D018040:Receptors, Neurokinin-1; D005070:Evans Blue; D010047:Ovalbumin; D015260:Neprilysin; D000241:Adenosine; D004205:Cromolyn Sodium