HYDROGEN-PEROXIDE ELICITS PULMONARY ARTERIAL RELAXATION AND GUANYLATE-CYCLASE ACTIVATION
HYDROGEN-PEROXIDE ELICITS PULMONARY ARTERIAL RELAXATION AND GUANYLATE-CYCLASE ACTIVATION
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DOI：
10.1152/ajpheart.1987.252.4.h721
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发表时间：
1987-04-01
影响因子：
--
通讯作者：
WOLIN, MS
中科院分区：
文献类型：
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作者：
BURKE, TM;WOLIN, MS
过氧化氢通过一种不依赖于内皮或前列腺素介体的机制，对预收缩的离体牛肺内动脉环产生浓度依赖性舒张作用。可溶性鸟苷酸环化酶活化的抑制剂亚甲蓝（10 μ M）显著减弱了对浓度高达100 μ M的过氧化氢的舒张反应。微摩尔浓度的过氧化氢引起与力降低相关的鸟苷3“，5”-环一磷酸的动脉水平的时间和浓度依赖性增加。可溶性鸟苷酸环化酶活性被酶促生成的过氧化氢显著激活，其激活方式与试验中存在的过氧化氢酶浓度最密切相关，激活机制受超氧阴离子和过氧化氢酶失活抑制。我们的数据与化合物I（过氧化物代谢过程中形成的一种过氧化氢酶）参与鸟苷酸环化酶激活机制最为一致。这种动脉舒张机制的性质表明，它可能有助于通过氧张力调节肺血管张力。
Hydrogen peroxide produces concentration-dependent relaxation of precontracted isolated bovine intrapulmonary arterial rings by a mechanism which is independent of the endothelium or prostaglandin mediators. Relaxant responses to hydrogen peroxide concentrations of up to 100 .mu.M were markedly attenuated by the inhibitor of soluble guanylate cyclase activation, methylene blue (10 .mu.M). Micromolar concentrations of hydrogen peroxide elicit time- and concentration-dependent increase in arterial levels of guanosine 3'',5''-cyclic monophosphate that are associated with decreases in force. Soluble guanylate cyclase activity is markedly activated by enzymatically generated hydrogen peroxide in a manner that is most closely associated with the concentration of catalase present in the assay, by a mechanism that is inhibited by superoxide anion and the inactivation of catalase. Our data are most consistent with the involvement of compound I, a species of catalase formed during the metabolism of peroxide, in the mechanism of guanylate cyclase activation. The nature of this mechanism of arterial relaxation suggests that it could contribute to the regulation of pulmonary vascular tone by oxygen tension.