Chronic hypoxia increases inducible NOS-derived nitric oxide in fetal guinea pig hearts.
Chronic hypoxia increases inducible NOS-derived nitric oxide in fetal guinea pig hearts.
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DOI：
10.1203/pdr.0b013e31818d6ad0
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发表时间：
2009-03
影响因子：
3.6
通讯作者：
Evans L
中科院分区：
文献类型：
--
作者：
Thompson L;Dong Y;Evans L
宫内缺氧影响胎儿生长和器官功能。测定诱导型一氧化氮合酶（iNOS）和神经型一氧化氮合酶（nNOS）的表达，以评估胎儿心脏对缺氧应激的反应。将妊娠豚鼠分别置于10.5%O_2低氧舱（HPX，n=17）和空气舱（NMX，n=17）中。取出麻醉的近足月胎儿的心脏。采用真实的时间PCR和Western分析分别检测胎儿左心室组织中缺氧诱导因子（HIF-1α、1β、2α、3α、iNOS、nNOS）mRNA和蛋白水平。在存在/不存在L-NIL（L-N6-（1-亚氨基乙基）-赖氨酸）（一种iNOS抑制剂）的情况下，测量妊娠母猪的心脏亚硝酸盐/硝酸盐水平。缺氧可显著增加胎儿心肌HIF-1α、HIF-2 α mRNA和HIF-1α蛋白的表达，但对HIF-3α、HIF-1 β mRNA的表达无明显影响。缺氧增加iNOS mRNA（5倍）和蛋白质（23%）水平，但对nNOS水平没有影响。HPX心脏中的亚硝酸盐/硝酸盐水平增加了2.5倍，而L-NIL降低了67± 14%。因此，上调iNOS衍生的NO生成是胎儿心脏对慢性缺氧应激反应的重要机制。
Intrauterine hypoxia impacts fetal growth and organ function. Inducible (iNOS) and neuronal NOS (nNOS) expression was measured to assess the response of fetal hearts to hypoxic stress. Pregnant guinea pigs were housed in a hypoxic chamber (10.5%O2 for 14d, hypoxia = HPX, n=17) or room air (NMX, n=17). Hearts of anesthetized near-term fetuses were removed. mRNA (hypoxia-inducible factor, HIF-1α, 1β, 2α, 3α, iNOS, nNOS) and protein levels (HIF-1α, iNOS, nNOS) of fetal cardiac left ventricles were quantified by real time PCR and Western analysis, respectively. Cardiac nitrite/nitrate levels were measured in the presence/absence of L-NIL (L-N6-(1-iminoethyl)-lysine), an iNOS inhibitor, administered to pregnant sows. Hypoxia significantly increased fetal cardiac HIF-1α and -2α mRNA, HIF-1α protein but not HIF-3α or -1β mRNA levels. Hypoxia increased both iNOS mRNA (by 5X) and protein (by 23%) levels but had no effect on nNOS levels. Nitrite/nitrate levels were increased in HPX hearts by 2.5X and decreased with L-NIL by 67±14%. Thus, upregulation of iNOS-derived NO generation is an important mechanism by which fetal hearts respond to chronic hypoxic stress.