Bernareggi M, Rossoni G, Berti F
Department of Pharmacology, Chemotherapy and Medical Toxicology, University of Milan, Italy.
Pharmacol Res. 1998 Jan;37(1):75-80. doi: 10.1006/phrs.1997.0266.
The compound 8-epi-prostaglandin F2 alpha (8-epi-PGF2 alpha), a F2-isoprostane formed mainly via a non-cyclooxygenase pathway, has been shown to constrict both human and guinea pig airway smooth muscle in vitro. We investigated whether this compound has any activity on bronchial resistance and plasma exudation in tracheal tissue of anaesthetised guinea pigs. 8-Epi-PGF2 alpha (12.5, 25 and 50 micrograms kg-1 i.v.) elicited a dose-dependent increase in intratracheal pressure. Diphenhydramine (2 mg kg-1 i.v.), indomethacin (1 mg kg-1 i.v.) and NG-nitro-L-arginine methyl ester (L-NAME, 10 mg kg-1 i.v.) did not affect the 8-epi-PGF2 alpha (25 micrograms kg-1 i.v.)-induced bronchoconstriction. On the contrary, while atropine (0.5 mg kg-1 i.v.) injected 10 min prior to 8-epi-PGF2 alpha (25 micrograms kg-1 i.v.) significantly reduced to 55% (P < 0.05) the increase in intratracheal pressure induced by the isoprostane, the selective thromboxane A2 receptor antagonist, ICI-192,605 (0.5 mg kg-1 i.v.) abolished it (95%, P < 0.001). Furthermore, 8-epi-PGF2 alpha (50, 100 and 200 micrograms kg-1 i.v.) increased plasma leakage, measured according to the Evans Blue dye technique, in tracheal tissue. This effect was particularly evident when 8-epi-PGF2 alpha was injected at the dose of 200 micrograms kg-1 i.v. (105% increase; P < 0.01) and it was markedly reduced by ICI-192,605 (0.5 mg kg-1 i.v.) (36%; P < 0.01) but not by diphenhydramine (2 mg kg-1 i.v.). In isolated perfused lungs, 8-epi-PGF2 alpha (2.5 micrograms ml-1 min-1 perfused for 2 min) increased the thromboxane A2 formation which was significantly reduced by ICI-192,605 (16 micrograms ml-1 min-1 perfused for 5 min) and abolished by indomethacin (1 microgram ml-1 min-1 perfused for 15 min). These data indicate that 8-epi-PGF2 alpha induces bronchoconstriction in guinea pig in vivo and that this effect, which seems to be related to activation of thromboxane A2 receptor, is associated to an augment of vascular permeability with plasma leakage in airway smooth muscle.
化合物8-表-前列腺素F2α（8-epi-PGF2α）是一种主要通过非环氧化酶途径形成的F2-异前列腺素，已显示在体外可使人和豚鼠气道平滑肌收缩。我们研究了该化合物对麻醉豚鼠气管组织中的支气管阻力和血浆渗出是否有任何作用。静脉注射8-表-前列腺素F2α（12.5、25和50微克/千克）可引起气管内压力呈剂量依赖性升高。苯海拉明（静脉注射2毫克/千克）、吲哚美辛（静脉注射1毫克/千克）和NG-硝基-L-精氨酸甲酯（L-NAME，静脉注射10毫克/千克）不影响8-表-前列腺素F2α（静脉注射25微克/千克）诱导的支气管收缩。相反，虽然在注射8-表-前列腺素F2α（25微克/千克）前10分钟静脉注射阿托品（0.5毫克/千克）可使异前列腺素诱导的气管内压力升高显著降低至55%（P<0.05），但选择性血栓素A2受体拮抗剂ICI-192,605（0.5毫克/千克）可消除该升高（95%，P<0.001）。此外，静脉注射8-表-前列腺素F2α（50、100和200微克/千克）可增加气管组织中的血浆渗漏，这是根据伊文思蓝染料技术测量的。当以200微克/千克的剂量静脉注射8-表-前列腺素F2α时，这种作用尤为明显（增加105%；P<0.01），并且ICI-192,605（0.5毫克/千克）可使其显著降低（36%；P<0.01），但苯海拉明（2毫克/千克）则不能。在离体灌注肺中，8-表-前列腺素F2α（以2.5微克/毫升·分钟的速度灌注2分钟）可增加血栓素A2的形成，ICI-192,605（以16微克/毫升·分钟的速度灌注5分钟）可使其显著降低，吲哚美辛（以1微克/毫升·分钟的速度灌注15分钟）可消除该形成。这些数据表明，8-表-前列腺素F2α在豚鼠体内诱导支气管收缩，并且这种作用似乎与血栓素A2受体的激活有关，与气道平滑肌中血浆渗漏导致的血管通透性增加有关。
