Seeger W, Ernst C, Walmrath D, Neuhof H, Roka L
Thromb Res. 1985 Dec 15;40(6):793-805. doi: 10.1016/0049-3848(85)90316-0.
In blood-free perfused isolated rabbit lungs increased availability of free arachidonic acid (AA), whether exogenously applied or released from the endogenous membrane phospholipid pool after different stimuli, causes an acute pulmonary artery pressor response and an increase in vascular permeability. Previous experiments suggested that the vasoconstriction is caused primarily by the cyclooxygenase product thromboxane (Tx) A2, whereas an increase in the capillary filtration coefficient must be ascribed to non-cyclooxygenase products of AA. The influence of BM 13.177, a non-prostanoic antagonist of TxA2- and endoperoxide-effects in platelets, on the AA-induced vascular effects in isolated rabbit lungs was investigated. BM 13.177 dose-dependently inhibited the pressor responses evoked by repetitive direct application of AA (IC50 approximately 10(-6) M) or by repetitive stimulation of endogenous AA-release with the calcium-ionophore A 23187 (IC50 approximately 10(-7) M), with maximum reduction of the pressor responses to less than 15%. The generation of TxA2 and of prostaglandin (PG) I2 evoked by these stimuli was, however, not altered. At a concentration of 10(-5) M BM 13.177 did not influence the capillary filtration coefficient, measured during venous pressure challenge, under baseline conditions and after stimulation with AA in presence of indomethacin.
BM 13.177 acts as TxA2/endoperoxide antagonist with dose-dependent inhibition of AA-induced vasoconstriction in the pulmonary vascular bed.
在无血灌注的离体兔肺中，游离花生四烯酸（AA）的可用性增加，无论其是外源性应用还是在不同刺激后从内源性膜磷脂池中释放，都会引起急性肺动脉升压反应和血管通透性增加。先前的实验表明，血管收缩主要由环氧化酶产物血栓素（Tx）A2引起，而毛细血管滤过系数的增加必须归因于AA的非环氧化酶产物。研究了BM 13.177（一种血小板中TxA2和内过氧化物作用的非前列腺素拮抗剂）对离体兔肺中AA诱导的血管效应的影响。BM 13.177剂量依赖性地抑制重复直接应用AA（半数抑制浓度约为10^(-6) M）或用钙离子载体A 23187重复刺激内源性AA释放（半数抑制浓度约为10^(-7) M）所诱发的升压反应，升压反应最大降低至小于15%。然而，这些刺激所诱发的TxA2和前列腺素（PG）I2的生成未改变。在10^(-5) M浓度下，BM 13.177在基线条件下以及在吲哚美辛存在下用AA刺激后，不影响静脉压力挑战期间测得的毛细血管滤过系数。
BM 13.177作为TxA2/内过氧化物拮抗剂，对肺血管床中AA诱导的血管收缩具有剂量依赖性抑制作用。
