Effect of a peptide leukotriene antagonist, ONO-1078 on antigen-induced airway microvascular leakage in actively sensitized guinea pigs.
We examined the effect of ONO-1078, a peptide leukotriene antagonist, on antigen-induced airway microvascular leakage in ovalbumin-sensitized guinea pigs. When guinea pigs were pretreated with mepyramine, ovalbumin challenge increased vascular permeability to Evans blue dye in trachea, main bronchi and intrapulmonary airways. Oral administration of ONO-1078 significantly reduced microvascular leakage in intrapulmonary airways at doses more than 3 mg/kg, but not in trachea. Moreover, oral administration of ONO-1078 significantly reduced SRS-A mediated microvascular leakage into all airway tissues and was more effective in intrapulmonary airways at 3 mg/kg. Simultaneously, ONO-1078 also inhibited SRS-A mediated bronchoconstriction. On the other hand, azelastine (10 mg/kg, p.o.), an anti-asthma agent, failed to inhibit microvascular leakage into the airways. These results suggest that peptide leukotrienes may be important mediators of airway microvascular leakage, and that the inhibitory effect of ONO-1078 on antigen-induced airway microvascular leakage in addition to the blockade of bronchoconstriction may have therapeutic implications for bronchial asthma.
Obata
T
T
Preclinical Research Department, Minase Research Institute, Ono Pharmaceutical Co., Ltd., Osaka, Japan.
Kobayashi
T
T
Okada
Y
Y
Nakagawa
N
N
Terawaki
T
T
Aishita
H
H
D000704:Analysis of Variance; D000818:Animals; D001886:Bordetella pertussis; D001993:Bronchodilator Agents / Q000494:pharmacology; D002199:Capillary Permeability / Q000187:drug effects*; D002867:Chromones / Q000494:pharmacology*; D005070:Evans Blue; D005119:Extravasation of Diagnostic and Therapeutic Materials; D006168:Guinea Pigs; D008297:Male; D010047:Ovalbumin; D010793:Phthalazines / Q000494:pharmacology; D012130:Respiratory Hypersensitivity / Q000503:physiopathology*; D012143:Respiratory Physiological Phenomena; D012137:Respiratory System / Q000187:drug effects* / Q000276:immunology; D013189:SRS-A / Q000037:antagonists & inhibitors*
D001993:Bronchodilator Agents; D002867:Chromones; D010793:Phthalazines; D013189:SRS-A; D005070:Evans Blue; D010047:Ovalbumin; C047681:pranlukast; C020976:azelastine