Inhaled cromoglycate reduces airway neurogenic inflammation via tachykinin antagonism.
To determine whether sodium cromoglycate (SCG) inhibits airway neurogenic inflammation and, if so, to elucidate the mechanism of its action, we studied plasma extravasation evoked by hypertonic saline in the rat trachea by measuring the amount of extravasated Evans blue dye. Inhalation of hypertonic saline (5-15% NaCl) produced microvascular leakage, an effect that was reduced by pretreatment with SCG in a dose-dependent manner. Inhaled SCG (10 mg/ml) for 2 min did not affect the basal vascular permeability, but significantly inhibited the 10% NaCl-induced plasma extravasation by 34%. SCG likewise inhibited the responses of microvascular leakage to substance P aerosols, whereas it was without effect on those to platelet activating factor aerosols. These results suggest that SCG inhibits airway neurogenic inflammation presumably via functional antagonism of tachykinins, and that this novel effect may be involved in the therapeutic efficacy of SCG in the treatment of airway inflammatory diseases including asthma.
Yamawaki
I
I
First Department of Medicine, Tokyo Women's Medical College, Japan.
Tamaoki
J
J
Takeda
Y
Y
Nagai
A
A
D000280:Administration, Inhalation; D000818:Animals; D018927:Anti-Asthmatic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D002199:Capillary Permeability / Q000187:drug effects; D004205:Cromolyn Sodium / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D007249:Inflammation / Q000188:drug therapy; D008297:Male; D010972:Platelet Activating Factor / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012462:Saline Solution, Hypertonic / Q000008:administration & dosage; D013047:Specific Pathogen-Free Organisms; D013373:Substance P / Q000494:pharmacology; D015320:Tachykinins / Q000037:antagonists & inhibitors*; D014132:Trachea / Q000098:blood supply / Q000187:drug effects* / Q000378:metabolism
D018927:Anti-Asthmatic Agents; D010972:Platelet Activating Factor; D012462:Saline Solution, Hypertonic; D015320:Tachykinins; D013373:Substance P; D004205:Cromolyn Sodium