Storme L, Rairigh R L, Parker T A, Kinsella J P, Abman S H
The Service de Medecine Neonatale, Hopital jeanne de Flandre, CHRU de Lille, France.
Pediatr Res. 1999 Apr;45(4 Pt 1):575-81. doi: 10.1203/00006450-199904010-00018.
To determine whether acute pulmonary hypertension in utero alters fetal pulmonary vascular reactivity, we compared pulmonary vasodilation with an endothelium-dependent agonist, acetylcholine, with that of an endothelium-independent agonist, 8-bromo-guanosine 3',5'-cylic monophosphate. Acute pulmonary hypertension was produced in chronically prepared, late-gestation fetal lambs by 3 repeated 30-minute partial occlusions of the ductus arteriosus (DA). The first DA compression increased LPA blood flow from 80 +/- 10 to 180 +/- 21 mL/min (p < 0.01) and decreased pulmonary vascular resistance. In contrast, LPA blood flow did not change and pulmonary vascular resistance increased by 25% during the third period of DA compression. Pulmonary vasodilation during acetylcholine infusion after serial DA compressions was decreased in comparison with the acetylcholine-induced vasodilator response achieved during the baseline period (fall in pulmonary vascular resistance = -49 +/- 7% (baseline) versus -25 +/- 5% after repeated DA compressions; p < 0.05). In contrast, the vasodilator response to 8-bromo-guanosine 3',5'-cylic monophosphate remained intact. To determine whether decreased nitric oxide (NO) production may contribute to altered vasoreactivity after acute pulmonary hypertension, repeated DA compressions were performed after treatment with a nonspecific NO synthase inhibitor (nitro-L-arginine). NO synthase inhibition blocked the pulmonary vasodilation during the first DA compression period, and repeated DA compressions after NO synthase inhibition did not further alter the hemodynamic response to DA compression. These findings support the hypothesis that brief hypertension due to DA compression impairs endothelium-dependent pulmonary vasodilation in the fetus, and that this may be due to decreased NO production.
为了确定子宫内急性肺动脉高压是否会改变胎儿肺血管反应性，我们比较了内皮依赖性激动剂乙酰胆碱与内皮非依赖性激动剂8-溴鸟苷3',5'-环磷酸的肺血管舒张作用。通过对动脉导管（DA）进行3次重复的30分钟部分闭塞，在长期制备的妊娠晚期胎羊中诱发急性肺动脉高压。第一次DA压迫使左肺动脉（LPA）血流从80±10增加至180±21 mL/min（p<0.01），并降低了肺血管阻力。相比之下，在第三次DA压迫期间，LPA血流未改变，肺血管阻力增加了25%。与基线期乙酰胆碱诱导的血管舒张反应相比，连续DA压迫后乙酰胆碱输注期间的肺血管舒张作用减弱（肺血管阻力下降=-49±7%（基线），重复DA压迫后为-25±5%；p<0.05）。相比之下，对8-溴鸟苷3',5'-环磷酸的血管舒张反应保持完整。为了确定一氧化氮（NO）生成减少是否可能导致急性肺动脉高压后血管反应性改变，在用非特异性NO合酶抑制剂（硝基-L-精氨酸）治疗后进行重复的DA压迫。NO合酶抑制阻断了第一次DA压迫期间的肺血管舒张，NO合酶抑制后重复的DA压迫未进一步改变对DA压迫的血流动力学反应。这些发现支持以下假设：DA压迫引起的短暂高血压会损害胎儿内皮依赖性肺血管舒张，这可能是由于NO生成减少所致。
