Shayevitz J R, McShane A J, Traystman R J, Gurtner G H
University of Michigan School of Medicine, Ann Arbor, 48109.
J Appl Physiol (1985). 1989 Apr;66(4):1921-6. doi: 10.1152/jappl.1989.66.4.1921.
The organic peroxide tert-butyl hydroperoxide (t-bu-OOH) induces pulmonary vasoconstriction by stimulating production of thromboxane in the rabbit lung, possibly by activating phospholipase A2. t-bu-OOH-induced vasoconstriction and thromboxane production is augmented by inhalational anesthetic agents, perhaps due to an effect of anesthetic agents on membrane lipids. To further investigate the mechanism of thromboxane generation, we studied the influence of the phospholipase A2 inhibitor, mepacrine, in a dose known to inhibit the enzyme in other systems, on t-bu-OOH-induced pulmonary arterial vasoconstriction. We found that 10(-4) M mepacrine completely inhibited t-bu-OOH-induced vasoconstriction. We also found that mepacrine inhibited arachidonic acid-induced pulmonary vasoconstriction but did not inhibit thromboxane productions. We also investigated the effect of mepacrine on two other pulmonary vasoconstrictors, angiotensin II (ANG II) and KCl, which do not act through arachidonic acid metabolites in the rabbit lung. Mepacrine inhibited both ANG-II and KCl-induced vasoconstriction. The inhibition by mepacrine of pulmonary vasoconstriction is reversible if the drug is washed out of the lung. This effect of mepacrine cannot be explained by phospholipase inhibition alone and is consistent with prevention of smooth muscle contraction.
有机过氧化物叔丁基过氧化氢（t-bu-OOH）通过刺激兔肺中血栓素的产生诱导肺血管收缩，可能是通过激活磷脂酶A2来实现的。吸入麻醉剂可增强t-bu-OOH诱导的血管收缩和血栓素生成，这可能是由于麻醉剂对膜脂质的作用。为了进一步研究血栓素生成的机制，我们研究了磷脂酶A2抑制剂米帕林在已知能在其他系统中抑制该酶的剂量下，对t-bu-OOH诱导的肺动脉血管收缩的影响。我们发现10^(-4)M米帕林完全抑制了t-bu-OOH诱导的血管收缩。我们还发现米帕林抑制花生四烯酸诱导的肺血管收缩，但不抑制血栓素的产生。我们还研究了米帕林对另外两种肺血管收缩剂血管紧张素II（ANG II）和氯化钾的影响，它们在兔肺中不通过花生四烯酸代谢物起作用。米帕林抑制了ANG-II和氯化钾诱导的血管收缩。如果将药物从肺中冲洗掉，米帕林对肺血管收缩的抑制作用是可逆的。米帕林的这种作用不能仅用磷脂酶抑制来解释，且与预防平滑肌收缩一致。
