4－氧－8－［对－（4－苯丁氧基）苯甲酰氨基］－2－（5－四唑基）－4H－1－苯并吡喃抑制抗原诱导的豚鼠气道收缩及微血管渗漏的作用

Effect of 4-oxo-8-[p-(4-phenylbutyloxy) benzoylamino]-2-(tetrazol-5-yl)-4H-1-benzopyran hemihydrate on antigen-induced airway constriction and microvascular leakage in guinea pigs

在扑尔敏预先处理的致敏豚鼠，白三烯拮抗剂４－氧－８－［对－（４－苯丁氧基）苯甲酰氨基］－２－（５－四唑基）－４Ｈ－１－苯并吡喃（ＯＮＯ－１０７８，０．０３，０．３ｍｇ·ｋｇ－１，ｉｖ）显著抑制抗原引起的肺内压增高，并完全抑制肺内气道中心部和外周部的依文思蓝渗出。肺内压与这两部位的染料渗出量呈正相关，但与气管和主支气管的染料渗出无相关性。在扑尔敏处理的肺条和气管条，ＯＮＯ－１０７８（１μｍｏｌ·Ｌ－１）仅部分抑制抗原诱导的收缩（４５．８％和３３．３％）。结果说明ＯＮＯ－１０７８抑制抗原诱导的气道收缩作用，至少部分通过抑制微血管渗漏，并主要作用在相对外周的气道。

This study was to examine the mecha-nism of the effect of 4-oxo-8-[p-(4-phenylbutyl-oxy) benzoylamino]-2-(tetrazol-5-yl)-4H-1-ben-zopyran hemihydrate (ONO-1078), a leukotriene an-tagonist, on ovalbumin(OA)-induced airway constric-tion in the actively sensitized guinea pigs. After thepretreatment with chlorpheniramine to blockhistamine responses, ONO-1078(0.03, 0.3 mg·kg-1,iv) remarkably inhibited the OA-induced increase inintrapulmonary pressure (IPP), and completely inhib-ited Evans blue extravasation in proximal and distalintrapulmonary airways (IPA). IPP was well correlatedwith Evans blue extravasation in either proximal ordistal IPA (r=0.49 and 0.53, P<0.01), but not withthat in trachea or main bronchi. In contrast,ONO-1078 (1μmol·L-1) only partially inhibitedOA-induced contraction in chlorpheniramine-pretreated and isolated lung parenchymal and trachealstrips (by 45.8% and 33.3% respectively). The resultsindicate that ONO-1078 antagonizes antigen-inducedairway constriction at least partly via an inhibition ofairway microvascular leakage, and mainly acts on rela-tively peripheral airways.