Tai H H, Chang W C, Liu Y, Fukuda S
Division of Medicinal Chemistry and Pharmaceutics, College of Pharmacy, University of Kentucky, Lexington 40536-0082.
Adv Exp Med Biol. 1990;273:211-24. doi: 10.1007/978-1-4684-5829-9_21.
Male rats were exposed to freshly generated cigarette smoke once daily for various lengths of time. Inhalation of smoke was verified by elevated levels of carboxyhemoglobin. Metabolism of arachidonate in the cardiovascular system to thromboxane and prostacyclin through the cyclooxygenase pathway and their further metabolism to 15-keto-derivatives, and to 12-hydroxyeicosatetraenoic acid (12-HETE) through lipoxygenase pathway was investigated. Synthesis of thromboxane and prostacyclin in platelets and aortas respectively was not changed within 8 weeks of smoke exposure. However, formation of 12-HETE in platelets was significantly increased after 4 weeks of smoke exposure. Catabolism of thromboxane and prostacyclin as determined by NAD(+)-dependent 15-hydroxyprostaglandin dehydrogenase activity was greatly decreased in lung but not in kidney and stomach following 4 weeks of smoke exposure. Increased 12-lipoxygenase activity in platelets may lead to stimulation of migration and proliferation of smooth muscle cells and to increased synthesis of leukotrienes in neutrophils. Decreased pulmonary prostaglandin catabolic activity may result in increase in circulating thromboxane/prostacyclin ratio and subsequently alteration of vascular homeostasis. The consequence of these biochemical changes may contribute to the development of atherosclerosis, thromboembolism and emphysema commonly found in smokers.
雄性大鼠每天暴露于新鲜产生的香烟烟雾中，持续不同时长。通过检测碳氧血红蛋白水平升高来证实烟雾吸入情况。研究了心血管系统中花生四烯酸通过环氧合酶途径代谢为血栓素和前列环素，以及它们进一步代谢为15-酮衍生物，和通过脂氧合酶途径代谢为12-羟基二十碳四烯酸（12-HETE）的情况。在烟雾暴露8周内，血小板和主动脉中血栓素和前列环素的合成分别没有变化。然而，烟雾暴露4周后，血小板中12-HETE的形成显著增加。烟雾暴露4周后，肺中由NAD(+)-依赖性15-羟基前列腺素脱氢酶活性所测定的血栓素和前列环素的分解代谢大大降低，但肾脏和胃中没有。血小板中12-脂氧合酶活性增加可能导致平滑肌细胞迁移和增殖受到刺激，并导致中性粒细胞中白三烯合成增加。肺中前列腺素分解代谢活性降低可能导致循环中血栓素/前列环素比值增加，进而改变血管稳态。这些生化变化的后果可能促成吸烟者中常见的动脉粥样硬化、血栓栓塞和肺气肿的发展。
