[Effect of sodium cromoglycate on airway vascular leakage caused by hypertonic saline in the rat trachea].
The action of the anti-asthmatic drug sodium cromoglycate (SCG) on airway inflammation remains uncertain. Using Evans blue dye as a maker of plasma leakage, we studied the effect of SCG on neurogenic vascular extravasation evoked by hypertonic saline (HTS) in the rat trachea. Inhalation of HTS (5-15%) caused a concentration-dependent increase in plasma leakage, but inhaled 0.9% NaCl had no effect. Inhalation of SCG did not affect the baseline level of vascular permeability, but it inhibited the effect of HTS in a dose-dependent manner: plasma extravasation induced by 10% NaCl was significantly reduced by 2 minutes of inhalation of SCG at concentrations of 10 and 50 mg/ml (p < 0.05 and p < 0.01, respectively). SCG (10 mg/ml), also inhibited the changes in microvascular permeability caused by aerosols of substance P (10(-4) M), whereas it did not affect the responses to aerosols of platelet-activating factor (3 x 10(-4) M). A similar dose of SCG did not significantly alter microvascular leakage caused by 5% NaCl. However, phosphoramidon, a selective inhibitor of neutral endopeptidase, potentiated the response to 5% NaCl, an effect that was inhibited by SCG (p < 0.05). These results suggest that SCG inhibits HTS-induced airway vascular permeability, presumably through a tachykinin-antagonist-like property, and that this inhibition is exaggerated when the activity of endogenous neutral endopeptidase is low.
Yamawaki
I
I
First Department of Medicine, Tokyo Women's Medical College, Japan.
Tamaoki
J
J
Takeda
Y
Y
Konno
K
K
D000818:Animals; D018927:Anti-Asthmatic Agents / Q000494:pharmacology*; D002199:Capillary Permeability / Q000187:drug effects*; D004205:Cromolyn Sodium / Q000494:pharmacology*; D007249:Inflammation; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012462:Saline Solution, Hypertonic; D014133:Tracheal Diseases / Q000139:chemically induced / Q000188:drug therapy*
D018927:Anti-Asthmatic Agents; D012462:Saline Solution, Hypertonic; D004205:Cromolyn Sodium