Effect of azelastine on platelet-activating factor and antigen-induced pleurisy in rats.
The interference of azelastine with pleurisy induced by antigen was investigated in actively sensitized rats. The antigenic challenge (ovalbumin, 12 micrograms/cavity) caused early plasma leakage, which peaked within 4 h, accompanied by intense neutrophil infiltration. Pleural exudate decayed 24 h after antigen provocation, when a long-lasting increase in the number of resident eosinophils was observed. Oral pretreatment with azelastine (1-10 mg/kg) dose dependently inhibited the vasopermeation (ED50 = 4.2 mg/kg) and reduced the pleural exudate (ED50 = 6.8 mg/kg) induced by the antigen. In contrast, azelastine (10 mg/kg) failed to modify the neutrophil influx observed at 4 h and the eosinophil accumulation detected at 24 h. Azelastine was also effective against rat pleurisy induced by either platelet-activating factor (PAF-acether), histamine or serotonin. It reduced exudation and the increase in the number of mononuclear cells, neutrophils and eosinophils observed 6 h after PAF-acether. Nevertheless, antagonism of PAF-acether may not be relevant to the inhibition observed in the present model of allergic pleurisy, as the inhibition was refractory to three distinct PAF-acether receptor antagonists. In contrast, like azelastine, the histamine H1 receptor antagonist meclizine and the dual histamine and serotonin receptor antagonist cyproheptadine blocked antigen-induced exudation and failed to interfere with cell influx. We conclude that the anti-exudatory activity of oral azelastine on antigen-induced pleurisy is consistent with it exerting direct effects against vasoactive amines, but is not related to an effect against leucocyte infiltration nor to its ability to inhibit PAF-acether.
Lima
M C
MC
Instituto Oswaldo Cruz, Departamento de Fisiologia e Farmacodinâmica, Rio de Janeiro, Brazil.
Martins
M A
MA
Perez
S A
SA
Silva
P M
PM
Cordeiro
R S
RS
Vargaftig
B B
BB
D000818:Animals; D000941:Antigens / Q000008:administration & dosage; D005260:Female; D006632:Histamine / Q000494:pharmacology; D006634:Histamine H1 Antagonists / Q000494:pharmacology; D007962:Leukocytes / Q000187:drug effects / Q000473:pathology; D008297:Male; D010047:Ovalbumin / Q000276:immunology; D010793:Phthalazines / Q000494:pharmacology*; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D010996:Pleural Effusion / Q000209:etiology / Q000473:pathology / Q000517:prevention & control; D010998:Pleurisy / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000494:pharmacology
D000941:Antigens; D006634:Histamine H1 Antagonists; D010793:Phthalazines; D010972:Platelet Activating Factor; D012701:Serotonin; D006632:Histamine; D010047:Ovalbumin; C020976:azelastine