Spannhake E W, Levin J L, Hyman A L, Kadowitz P J
Prostaglandins. 1981 Feb;21(2):267-75. doi: 10.1016/0090-6980(81)90144-1.
In anesthetized, vagotomized an mechanically ventilated cats, we investigated the bronchodilatory activity of the PGI2 metabolite, 6-keto-PGE1, relative to PGI2 and PGE2. In a range of doses from 0.3-10.0 microgram, i.v. injection of 6-keto-PGE1 produced a dose-related decrease in central airway resistance (RL) in animals bronchoconstricted by 5-HT. This effect on RL was 3-10 times greater than that produced by i.v. PGI2. At the lower doses, 6-keto-PGE1 was also more potent than PGI2 in increasing dynamic lung compliance; their effects upon semi-static compliance were not significantly different. Comparison of the bronchopulmonary effects of the two prostanoids did not show any consistent difference in their temporal patterns. In contrast to PGI2 or PGE2, 6-keto-PGE1 had minimal pulmonary vasomotor activity. Inhibition of the cyclooxygenase pathway with sodium meclofenamate had no effect on the bronchopulmonary actions of 6-keto-PGE1 or on its duration of action. These data indicate that 6-keto-PGE1 is a more potent bronchodilator than PGI2 in the cat. They further suggest that conversion of PGI2 to 6-keto-PGE1, if it occurs to an appreciable extent in the lung in vivo, could enhance bronchodilatory activity.
在麻醉、切断迷走神经并机械通气的猫身上，我们研究了前列环素（PGI2）的代谢产物6-酮-前列腺素E1（6-keto-PGE1）相对于PGI2和前列腺素E2（PGE2）的支气管舒张活性。静脉注射剂量范围为0.3 - 10.0微克的6-酮-前列腺素E1，可使因5-羟色胺（5-HT）引起支气管收缩的动物的中心气道阻力（RL）呈剂量依赖性降低。这种对RL的作用比静脉注射PGI2所产生的作用大3至10倍。在较低剂量时，6-酮-前列腺素E1在增加动态肺顺应性方面也比PGI2更有效；它们对半静态顺应性的影响没有显著差异。比较这两种前列腺素的支气管肺效应，未发现它们在时间模式上有任何一致的差异。与PGI2或PGE2不同，6-酮-前列腺素E1的肺血管舒缩活性极小。用甲氯芬那酸钠抑制环氧化酶途径对6-酮-前列腺素E1的支气管肺作用及其作用持续时间均无影响。这些数据表明，在猫体内，6-酮-前列腺素E1是比PGI2更有效的支气管扩张剂。它们进一步表明，如果PGI2在体内肺中能大量转化为6-酮-前列腺素E1，可能会增强支气管舒张活性。
