NO and H2O2 mechanisms of guanylate cyclase activation in oxygen-dependent responses of rat pulmonary circulation.
NO and H2O2 mechanisms of guanylate cyclase activation in oxygen-dependent responses of rat pulmonary circulation.
复制标题
大鼠肺循环氧依赖性反应中鸟苷酸环化酶激活的 NO 和 H2O2 机制。
DOI：
10.1152/ajplung.1995.268.4.l546
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发表时间：
1995
期刊：
影响因子：
--
通讯作者：
Burke-Wolin,T
中科院分区：
文献类型：
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作者：
Monaco,JA;Burke-Wolin,T
肺缺氧性血管收缩似乎有内皮依赖性和非内皮依赖性调节途径。我们之前已经描述了一种在离体肺动脉中激活鸟苷环化酶的机制，该机制是由平滑肌和氧张力依赖的。在这项研究中，我们研究了这一机制，包括过氧化氢酶代谢过氧化氢，以及它与内皮来源的一氧化氮在氧分压调节肺动脉压(PAP)中的关系。利用选择性激活鸟苷环化酶两种不同机制的探针，我们在缓冲灌流的大鼠离体肺中发现，NO生成抑制剂100微米的硝基L精氨酸使基线PAP从4.8+/-0.6毫米汞柱增加到6.0+/-0.6毫米汞柱，低氧PAP从6.8+/-0.8毫米汞柱增加到8.56+/-0.6毫米汞柱。过氧化氢酶代谢H_2O_2的抑制剂氨基三唑(AT)也使PAP从4.5+/-0.9升至6.1+/-2.0毫米汞柱(P<；OR=0.05)，使缺氧性PAP从6.0+/-1.7升至8.7+/-2.7毫米汞(P<；OR=0.05)。此外，虽然NLA不影响复氧时发生的血管扩张，但AT抑制了对复氧的即时反应。在NLA和AT同时存在的情况下，基础PAP从4.25+/-0.8升至9.9+/-0.92毫米汞柱(P<；OR=0.05)，但低氧对PAP无显著影响，复氧反应受到抑制。这些数据表明，在常氧条件下，NO和H_2O_2-过氧化氢酶机制对维持低PAP的作用程度相似。任何一种介质的去除都可能导致缺氧性血管收缩。
Pulmonary hypoxic vasoconstriction appears to have both endothelium-dependent and -independent regulatory pathways. We have previously described a mechanism of guanylate cyclase activation in isolated pulmonary arteries that is smooth muscle contained and oxygen tension dependent. In this study we examine this mechanism, involving H2O2 metabolism by catalase, and its relationship to endothelial-derived nitric oxide in the regulation of pulmonary artery pressure (PAP) by oxygen tension. Using probes selective for these two distinct mechanisms of guanylate cyclase activation, we found in the isolated buffer-perfused rat lung that 100 microM nitro-L-arginine (NLA), an inhibitor of NO formation, increased baseline PAP from 4.8 +/- 0.6 to 6.0 +/- 0.6 mmHg and hypoxic PAP from 6.8 +/- 0.8 to 8.56 +/- 0.6 mmHg. Aminotriazole (AT), an inhibitor of H2O2 metabolism by catalase, also increased PAP from 4.5 +/- 0.9 to 6.1 +/- 2.0 mmHg (P < or = 0.05) and hypoxic PAP from 6.0 +/- 1.7 to 8.7 +/- 2.7 mmHg (P < or = 0.05). Additionally, while NLA did not affect the vasodilation that occurs upon reoxygenation, AT inhibited the immediate response to reoxygenation. In the presence of both NLA and AT, baseline PAP increased from 4.25 +/- 0.8 to 9.9 +/- 0.92 mmHg (P < or = 0.05), but hypoxia did not significantly increase PAP and the reoxygenation response was inhibited. These data suggest that both NO and H2O2-catalase mechanisms contribute to a similar degree to maintain low PAP under normoxic conditions. The removal of either mediator may contribute to hypoxic vasoconstriction.