Arakawa H, Kawikova I, Löfdahl C G, Lötvall J
Division of Clinical Pharmacology (Department of Pharmacology), Göteborg University, Sweden.
Eur J Pharmacol. 1992 Dec 15;229(2-3):131-6. doi: 10.1016/0014-2999(92)90546-g.
We studied the effects of indomethacin (10 mg/kg i.v.), a cyclooxygenase inhibitor, and OKY-046 (1, 10 and 30 mg/kg i.v.), a selective thromboxane synthetase inhibitor, on airflow obstruction and airway plasma exudation induced by bradykinin (150 nmol) instilled by the airway route to anesthetized guinea pigs. To do this, we studied changes in lung resistance (RL) and extravasation of Evans Blue dye respectively. Instilled bradykinin produced an immediate and marked increase in RL which peaked at approximately 30 s. We also observed a delayed increase in RL, reaching a second peak at approximately 3 min. Bradykinin produced airway plasma exudation at all airway levels, measured as extravasation of Evans Blue dye. Indomethacin significantly inhibited both the immediate and the delayed increase in RL after bradykinin. OKY-046 had a similar significant and dose-dependent inhibitory effect on these responses. In addition, both drugs inhibited bradykinin-induced Evans blue dye extravasation in intrapulmonary airways. Bradykinin instilled by the airway route significantly decreased systemic blood pressure but this effect was not altered in animals pretreated with either indomethacin or OKY-046. We conclude that the bronchoconstrictor response and airway plasma exudation induced by instilled-bradykinin may be mediated in part via thromboxane A2 generation.
我们研究了环氧化酶抑制剂吲哚美辛（静脉注射10毫克/千克）和选择性血栓素合成酶抑制剂OKY - 046（静脉注射1、10和30毫克/千克）对气道途径向麻醉豚鼠滴注缓激肽（150纳摩尔）所诱导的气流阻塞和气道血浆渗出的影响。为此，我们分别研究了肺阻力（RL）的变化和伊文思蓝染料的渗出情况。滴注缓激肽后，RL立即显著增加，在约30秒时达到峰值。我们还观察到RL的延迟增加，在约3分钟时达到第二个峰值。缓激肽在所有气道水平均引起气道血浆渗出，以伊文思蓝染料的渗出量来衡量。吲哚美辛显著抑制缓激肽后RL的即时和延迟增加。OKY - 046对这些反应具有类似的显著且剂量依赖性的抑制作用。此外，两种药物均抑制缓激肽诱导的肺内气道伊文思蓝染料渗出。气道途径滴注缓激肽显著降低全身血压，但在用吲哚美辛或OKY - 046预处理的动物中，这种作用未改变。我们得出结论，滴注缓激肽所诱导的支气管收缩反应和气道血浆渗出可能部分通过血栓素A2的生成介导。
