Peroxynitrite inhibits relaxation and induces pulmonary artery muscle contraction in the newborn rat
Peroxynitrite inhibits relaxation and induces pulmonary artery muscle contraction in the newborn rat
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DOI：
10.1016/j.freeradbiomed.2004.07.029
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发表时间：
2004-11-01
影响因子：
7.4
通讯作者：
Tanswell, AK
中科院分区：
文献类型：
--
作者：
Belik, J;Jankov, RP;Tanswell, AK
一氧化氮（NO）与超氧阴离子反应形成过氧亚硝酸根阴离子（ONOO-），这是一种在成年大鼠中具有肺血管扩张特性的分子。本研究的目的是比较ONOO-对新生大鼠（4-7天）、幼年大鼠（14天）和成年大鼠肺内动脉的影响。血栓素A（2）（TXA（2））类似物（U46619）预刺激后，新生血管对ONOO-诱导的肌肉收缩比幼年和成年血管更敏感。布洛芬、内皮素B受体阻断剂（A-192621）或rho激酶特异性抑制剂（Y27632）可消除过氧亚硝基阴离子诱导的新生血管收缩（所有p < 0.01）。在KCl刺激和TXA（2）受体阻断后，ONOO通过刺激内皮和诱导型一氧化氮合酶诱导新生血管中NO依赖性肌松。而ONOO-存在时，肺动脉对内皮依赖性刺激的舒张反应显著降低（p < 0.01）。最后，暴露于ONOO-的新生儿而非成人肺动脉显示8-异前列烷的产生增加了10倍，8-异前列烷是ONOO-诱导收缩的可能介质。我们的结论是，暴露于ONOO（-）导致新生儿肺内动脉的独特反应，其特征是8-异前列烷生成增加，我们认为这是其血管收缩作用的原因。这种独特的反应可能使新生儿比老年动物更容易受到ONOO诱导的肺动脉高压的影响。(C)2004爱思唯尔公司All rights reserved.
Nitric oxide (NO) reacts with superoxide anion to form the peroxynitrite anion (ONOO-), a molecule with pulmonary vasodilator properties in the adult rat. The purpose of this study was to compare the effects of ONOO- on intrapulmonary arteries from the newborn (days 4-7), juvenile (day 14), and adult rat. Following thromboxane A(2) (TXA(2)) analogue (U46619) prestimulation, newbom vessels were more sensitive to ONOO--induced muscle contraction, compared to both the juvenile and the adult vessels. Peroxynitrite-induced contraction in newborn vessels was abrogated by ibuprofen, an endothelin B-receptor blocker (A-192621), or a rho-kinase-specific inhibitor (Y27632) (all p < 0.01). Following KCI stimulation and TXA(2) receptor blockade, ONOO- induced NO-dependent muscle relaxation in newbom vessels via stimulation of the endothelial and inducible nitric oxide synthases. However, in the presence of ONOO-, the pulmonary artery relaxation response to endothelium-dependent stimulation was significantly reduced (p < 0.01). Finally, newbom but not adult pulmonary arteries exposed to ONOO- showed a 10-fold increase in 8-isoprostane production, a possible mediator of ONOO--induced contraction. We conclude that exposure to ONOO(-)results in a unique response in newbom intrapulmonary arteries characterized by increased 8-isoprostane generation, which we believe is responsible for its vasoconstrictor effect. This unique response potentially renders the newbom more susceptible to ONOO--induced pulmonary hypertension than older animals. (C) 2004 Elsevier Inc. All rights reserved.