Burghuber O C, Morganroth M L, Stenmark K R, Morris K G, Reeves J T, Voelkel N F
Wien Klin Wochenschr. 1986 Feb 21;98(4):113-7.
The mechanism of hypoxic pulmonary vasoconstriction is still unclear. Since leukotrienes are pulmonary vasoconstrictors and lung cells are able to produce leukotrienes, it has been proposed that leukotrienes are mediators of hypoxic pulmonary vasoconstriction and then inhibition of their synthesis should block hypoxic pressure responses. In order to test this hypothesis we investigated whether diethylcarbamazine (DEC), a known leukotriene synthesis blocker, blocks hypoxic pulmonary vasoconstriction in isolated rat lungs. DEC blocked ongoing and subsequent hypoxic pressure responses in a relatively specific and dose-dependent fashion. We therefore extended our observations to awake rats and found that DEC reversibly inhibited acute hypoxic pulmonary vasoconstriction. Furthermore, pulmonary hypertension and right ventricular hypertrophy in rats exposed to chronic hypobaric hypoxia could be prevented by DEC treatment. From these data we conclude that DEC inhibits both acute and chronic hypoxic pulmonary vasoconstriction. Thus, leukotrienes could be important mediators of hypoxic pulmonary vasoconstriction.
低氧性肺血管收缩的机制仍不清楚。由于白三烯是肺血管收缩剂且肺细胞能够产生白三烯，因此有人提出白三烯是低氧性肺血管收缩的介质，那么抑制其合成应该能阻断低氧压力反应。为了验证这一假设，我们研究了已知的白三烯合成阻滞剂乙胺嗪（DEC）是否能阻断离体大鼠肺的低氧性肺血管收缩。DEC以相对特异且剂量依赖的方式阻断持续的及随后的低氧压力反应。因此，我们将观察扩展到清醒大鼠，发现DEC可可逆性抑制急性低氧性肺血管收缩。此外，DEC治疗可预防暴露于慢性低压低氧环境的大鼠的肺动脉高压和右心室肥大。根据这些数据我们得出结论，DEC可抑制急性和慢性低氧性肺血管收缩。因此，白三烯可能是低氧性肺血管收缩的重要介质。
