Mitochondrial oxidant stress increases PDE5 activity in persistent pulmonary hypertension of the newborn.
Mitochondrial oxidant stress increases PDE5 activity in persistent pulmonary hypertension of the newborn.
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DOI：
10.1016/j.resp.2010.08.018
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发表时间：
2010-12-31
影响因子：
2.3
通讯作者：
Steinhorn RH
中科院分区：
文献类型：
--
作者：
Farrow KN;Wedgwood S;Lee KJ;Czech L;Gugino SF;Lakshminrusimha S;Schumacker PT;Steinhorn RH
在肺血管系统中，磷酸二酯酶-5(PDE5)降解cGMP并抑制一氧化氮介导的cGMP依赖的血管松弛。我们先前报道，与对照羔羊相比，100%O2的通气会增加肺动脉高压羔羊(PPHN)的肺动脉(PA)PDE5活性。在本研究中，PPHN羔羊的PA平滑肌细胞(PASMC)与对照PASMC相比，基础PDE5活性增加，cGMP对NO的反应性降低，线粒体基质氧化应激增加。高氧(24小时)使PPHN和对照组PASMC的PDE5活性和线粒体基质氧化应激水平高于基线水平。线粒体靶向过氧化氢酶降低PPHN PASMC在基线和高氧后PDE5活性。同样，用100%O2通风的PPHN羔羊，过氧化氢酶处理降低了PA中PDE5活性，增加了cGMP。我们得出结论，PPHN PASMC的基础PDE5活性和氧化应激增加，清除H_2O_2足以阻止氧化剂介导的PPHN PDE5活性的增加。
In the pulmonary vasculature, phosphodiesterase-5 (PDE5) degrades cGMP and inhibits nitric oxide-mediated, cGMP-dependent vasorelaxation. We previously reported that ventilation with 100% O2 increased PDE5 activity in pulmonary arteries (PA) of pulmonary hypertension lambs (PPHN) more than in control lambs. In the present study, PA smooth muscle cells (PASMC) from PPHN lambs had increased basal PDE5 activity, decreased cGMP-responsiveness to NO, and increased mitochondrial matrix oxidant stress compared to control PASMC. Hyperoxia (24h) increased PDE5 activity and mitochondrial matrix oxidant stress above baseline to a similar degree in PPHN and control PASMC. Mitochondrially-targeted catalase decreased PDE5 activity at baseline and after hyperoxia in PPHN PASMC. Similarly, catalase treatment of PPHN lambs ventilated with 100% O2 decreased PDE5 activity and increased cGMP in PA. We conclude that baseline PDE5 activity and oxidative stress is increased in PPHN PASMC, and scavenging H2O2 is sufficient to block oxidant-mediated increases in PDE5 activity in PPHN.
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影响因子：
158.5
作者：
Clark, RH;Kueser, TJ;Kinsella, JP
通讯作者：
Kinsella, JP
DOI：
10.1152/ajplung.90205.2008
发表时间：
2008-08-01
影响因子：
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作者：
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DOI：
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发表时间：
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影响因子：
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作者：
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影响因子：
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作者：
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影响因子：
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作者：
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