Dozen M, Yamaki K, Oh-Ishi S
Department of Pharmacology, School of Pharmaceutical Sciences, Kitasato University, Tokyo, Japan.
Jpn J Pharmacol. 1989 Sep;51(1):101-5. doi: 10.1254/jjp.51.101.
As previously reported, pretreatment with captopril significantly enhanced pleural exudation of rat carrageenin-induced pleurisy. However, in high molecular weight kininogen-deficient rats (B/N-Katholiek), the pleural exudate volume was significantly less than that of the normal strain (B/N-Kitasato), and captopril pretreatment did not enhance exudation. In the present study, the following additional evidences were demonstrated: 1) Captopril did not increase 6-keto-PGF1 alpha level in the deficient strain, but it was significantly increased in the normal strain after captopril treatment; 2) simultaneous administration of soybean trypsin inhibitor with carrageenin markedly suppressed the exudate volume and levels of 6-keto-PGF1 alpha in the normal strain; and 3) indomethacin also suppressed pleural fluid accumulation and the production of arachidonate metabolites. These data suggest that carrageenin causes intrinsic kinin-release through the activation of plasma kallikrein and then in turn, the kinin stimulates the production of arachidonic acid metabolites. Thus these products and kinin may interact to induce more plasma exudation in carrageenin inflammation. The results also indicate that captopril uncovers the effects of bradykinin on exudation and stimulation of arachidonate metabolite production; otherwise, the biological effect of kinin is too slight to produce a clear effect at the initial phase of the inflammation.
如先前报道，卡托普利预处理可显著增强大鼠角叉菜胶诱导胸膜炎的胸膜渗出。然而，在高分子量激肽原缺陷大鼠（B/N-Katholiek）中，胸膜渗出液体积显著小于正常品系（B/N-Kitasato），且卡托普利预处理并未增强渗出。在本研究中，还证实了以下额外证据：1）卡托普利未增加缺陷品系中6-酮-前列腺素F1α水平，但在正常品系中卡托普利处理后该水平显著升高；2）角叉菜胶与大豆胰蛋白酶抑制剂同时给药显著抑制正常品系中的渗出液体积和6-酮-前列腺素F1α水平；3）吲哚美辛也抑制胸腔积液积聚和花生四烯酸代谢产物的产生。这些数据表明，角叉菜胶通过激活血浆激肽释放酶导致内源性激肽释放，进而激肽刺激花生四烯酸代谢产物的产生。因此，这些产物和激肽可能相互作用，在角叉菜胶炎症中诱导更多血浆渗出。结果还表明，卡托普利揭示了缓激肽对渗出和花生四烯酸代谢产物产生的刺激作用；否则，在炎症初始阶段激肽的生物学效应过于轻微，无法产生明显作用。
