Inhibition by azelastine of the effects of platelet-activating factor in lungs from actively sensitised guinea-pigs.
The effect of azelastine on platelet-activating factor (PAF)-induced bronchoconstriction and mediator release in isolated lungs from actively sensitised guinea-pigs was investigated. Guinea-pigs were actively sensitised with two s.c. injections of 10 micrograms ovalbumin in 1 mg Al (OH)3 at a 2-week interval. One week after the second injection, the lungs were removed and challenged intra-arterially with PAF or arachidonic acid. In some experiments lungs from non-immunised guinea-pigs were injected with PAF or histamine. Bronchoconstriction, the release of thromboxane (TX)B2 or leukotriene (LT)-like material and the histamine content of the effluent were evaluated. Azelastine was given s.c. at 10 or 100 micrograms/kg, 4 h before lung removal. Azelastine (100 micrograms/kg) did not inhibit PAF-induced bronchoconstriction and mediator release from lungs from non-immunised guinea-pigs. In contrast, the hyperresponsiveness to 1 ng PAF observed in lungs from actively sensitised animals was dose dependently inhibited by azelastine. Azelastine did not reduce the histamine-induced bronchoconstriction and consequent TXB2 release from lungs from immunised guinea-pigs, indicating that the protective effect exerted against hyperresponsiveness to PAF was not due to histamine antagonism. Azelastine also reduced arachidonic acid-induced bronchoconstriction and LT-like material release from sensitised lungs, regardless of the presence of indomethacin. These results suggest that inhibition of lung hyperresponsiveness to PAF by azelastine may result from an interference with leukotriene synthesis.
Pretolani
M
M
Unité de Pharmacologie Cellulaire-Unité Associée Institut Pasteur/INSERM No. 285, Paris, France.
Lefort
J
J
Venco
C
C
Perrisoud
D
D
Vargaftig
B B
BB
D000818:Animals; D016718:Arachidonic Acid / Q000494:pharmacology; D016084:Bronchoconstriction / Q000187:drug effects; D006168:Guinea Pigs; D006632:Histamine / Q000494:pharmacology; D007114:Immunization; D007269:Injections, Intra-Arterial; D015289:Leukotrienes / Q000378:metabolism; D008168:Lung / Q000187:drug effects* / Q000502:physiology; D008297:Male; D010047:Ovalbumin / Q000008:administration & dosage; D010793:Phthalazines / Q000494:pharmacology*; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D011651:Pulmonary Artery; D013929:Thromboxane B2 / Q000378:metabolism
D015289:Leukotrienes; D010793:Phthalazines; D010972:Platelet Activating Factor; D010975:Platelet Aggregation Inhibitors; D016718:Arachidonic Acid; D013929:Thromboxane B2; D006632:Histamine; D010047:Ovalbumin; C020976:azelastine