Okazawa A, Kawikova I, Cui Z H, Skoogh B E, Lötvall J
Department of Respiratory Medicine and Allergology, Institute of Heart and Lung Diseases, Goteborg University, Gothenburg, Sweden.
Am J Respir Crit Care Med. 1997 Feb;155(2):436-41. doi: 10.1164/ajrccm.155.2.9032175.
8-Epi-prostaglandin F2alpha (8-epi-PGF2alpha) is an F2-isoprostane formed mainly via noncyclooxygenase pathways in vivo. We investigated whether 8-epi-PGF2alpha has any effect on airflow obstruction and plasma exudation in vivo. Airflow obstruction was quantified by measuring lung resistance (RL) in anesthetized and ventilated guinea pigs, and plasma exudation was quantified by the Evans Blue dye method (20 mg/kg intravenously). Intratracheal instillation of 8-epi-PGF2alpha (1 nmol or 10 nmol) caused dose-related increases in RL. Furthermore, the higher dose of 8-epi-PGF2alpha produced Evans Blue dye extravasation in main bronchi and intrapulmonary airways. A prostanoid TP-receptor antagonist, BAY u3405 (1 mg/kg intravenously), abolished the airway effects of 8-epi-PGF2alpha (10 nmol). A thromboxane A2 (TxA2) synthase inhibitor, OKY-406 (30 mg/kg intravenously), significantly attenuated these effects of 8-epi-PGF2alpha (10 nmol). The level of TxB2, a stable TxA2 metabolite, increased in bronchoalveolar lavage fluid (BALF) after 8-epi-PGF2alpha instillation. We conclude that 8-epi-PGF2alpha causes airflow obstruction and plasma exudation in vivo. This effect may be mediated primarily via prostanoid TP-receptors, and a secondary generation of TxA2 may be involved in part of the airway responses in 8-epi-PGF2alpha in the guinea pig.
8-表-前列腺素F2α（8-epi-PGF2α）是一种主要通过体内非环氧化酶途径形成的F2-异前列腺素。我们研究了8-epi-PGF2α在体内对气流阻塞和血浆渗出是否有任何影响。通过测量麻醉和通气豚鼠的肺阻力（RL）来量化气流阻塞，并用伊文思蓝染料法（静脉注射20mg/kg）量化血浆渗出。气管内滴注8-epi-PGF2α（1nmol或10nmol）导致RL呈剂量相关增加。此外，较高剂量的8-epi-PGF2α在主支气管和肺内气道产生伊文思蓝染料外渗。一种前列腺素TP受体拮抗剂BAY u3405（静脉注射1mg/kg）消除了8-epi-PGF2α（10nmol）的气道效应。一种血栓素A2（TxA2）合酶抑制剂OKY-406（静脉注射30mg/kg）显著减弱了8-epi-PGF2α（10nmol）的这些效应。8-epi-PGF2α滴注后，支气管肺泡灌洗液（BALF）中稳定的TxA2代谢产物TxB2水平升高。我们得出结论，8-epi-PGF2α在体内导致气流阻塞和血浆渗出。这种效应可能主要通过前列腺素TP受体介导，并且TxA2的二次生成可能部分参与豚鼠8-epi-PGF2α的气道反应。
