CHRONIC NITRIC-OXIDE INHIBITION IN-UTERO PRODUCES PERSISTENT PULMONARY-HYPERTENSION IN NEWBORN LAMBS
CHRONIC NITRIC-OXIDE INHIBITION IN-UTERO PRODUCES PERSISTENT PULMONARY-HYPERTENSION IN NEWBORN LAMBS
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DOI：
10.1172/jci117281
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发表时间：
1994-06-01
影响因子：
15.9
通讯作者：
SOIFER, SJ
中科院分区：
文献类型：
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作者：
FINEMAN, JR;WONG, J;SOIFER, SJ
新生儿持续性肺动脉高压（PPHN）与慢性宫内事件相关。急性一氧化氮（NO）抑制减弱了出生时肺血流量的正常增加。我们研究了子宫内慢性NO抑制是否会导致持续性肺动脉高压。11只胎羔接受连续输注n - ω -硝基- l -精氨酸（一种NO合成抑制剂）或0.9%生理盐水。在输注前，乙酰胆碱（依赖于内源性NO的产生）和硝普钠（其自身释放NO）产生有效的肺血管舒张。在注射10.5 +/- 1.5 d后，乙酰胆碱对n - ω -硝基- l -精氨酸处理的胎儿羔羊没有产生肺血管扩张，但对盐水处理的胎儿羔羊有；硝普钠对两组肺血管均有舒张作用。在出生后立即，妊娠140天，在3小时的研究期间，n - ω -硝基- l -精氨酸处理的羔羊平均肺动脉压没有下降；与盐处理羔羊相比，肺血流量的增加和肺血管阻力的降低明显减弱。这些血流动力学紊乱被l -精氨酸逆转。肺循环未见解剖异常。子宫内慢性NO抑制再现了许多PPHN的生理紊乱。导致内皮功能障碍和NO抑制的宫内事件可导致PPHN的生理紊乱。
Persistent pulmonary hypertension of the newborn (PPHN) is associated with chronic intrauterine events. Acute nitric oxide (NO) inhibition attenuates the normal increase in pulmonary blood flow at birth. We investigated whether chronic NO inhibition in utero causes persistent pulmonary hypertension. 11 fetal lambs received either a continuous infusion of N-omega-nitro-L-arginine (an NO synthesis inhibitor) or 0.9% saline. Before infusion, acetylcholine (dependent upon endogenous NO production) and sodium nitroprusside (which releases its own NO) produced potent pulmonary vasodilation. After 10.5 +/- 1.5 d of infusion, acetylcholine did not produce pulmonary vasodilation in N-omega-nitro-L-arginine-treated fetal lambs, but did in saline-treated fetal lambs; sodium nitroprusside produced pulmonary vasodilation in both groups. Immediately after birth, at 140 d of gestation, during the 3-h study period, mean pulmonary arterial pressure did not decrease in N-omega-nitro-L-arginine-treated lambs; the increase in pulmonary blood flow and decrease in pulmonary vascular resistance were markedly attenuated compared to saline-treated lambs. These hemodynamic derangements were reversed by L-arginine. There were no anatomic abnormalities in the pulmonary circulation. Chronic NO inhibition in utero reproduces many of the physiologic derangements of PPHN. Intrauterine events which result in endothelial dysfunction and inhibition of NO mag produce the physiologic derrangements of PPHN.