Martinez A, Padbury J, Shames L, Evans C, Humme J
Department of Pediatrics, UCLA School of Medicine, Harbor-UCLA Medical Center, Torrance 90509.
Pediatr Res. 1988 Apr;23(4):343-7. doi: 10.1203/00006450-198804000-00001.
The effect of opiate receptor blockade on the plasma catecholamine response to hypoxemia was studied in seven chronically catheterized fetal lambs in utero. All animals underwent treatment with hypoxia alone, naloxone infusion alone (2 mg/kg) and hypoxia with naloxone at four different dosages (0.1, 0.5, 1.0, and 2.0 mg/kg). Maternal and fetal hypoxia was maintained for 20 min. There were no differences noted in the degree of hypoxemia or acidemia between the different hypoxia treatment groups. Hypoxia increased both norepinephrine and epinephrine plasma levels in all fetal sheep studied. We found a dose-dependent increase in plasma epinephrine levels in response to naloxone infusion during hypoxia. Plasma epinephrine level by 20 min of hypoxia with the 0.1 mg/kg naloxone dose (geometric mean 5366 pg/ml) was significantly more than with hypoxia alone (997 pg/ml). Naloxone at the other doses did not alter the epinephrine responses. There was no augmentation of plasma norepinephrine levels by naloxone at any dose studied. Thus, naloxone augmented the plasma epinephrine response to hypoxia in fetal sheep suggesting that the opiate peptides act as modulators of the sympathoadrenal system. The naloxone dose response differences observed in this study suggest this modulation is largely by antagonism of mu-receptors.
在七只慢性插管的宫内胎羊中研究了阿片受体阻断对低氧血症引起的血浆儿茶酚胺反应的影响。所有动物均分别接受单纯低氧处理、单纯纳洛酮输注（2mg/kg）以及四种不同剂量（0.1、0.5、1.0和2.0mg/kg）纳洛酮与低氧联合处理。母体和胎儿低氧状态维持20分钟。不同低氧处理组之间的低氧血症或酸血症程度无差异。在所研究的所有胎羊中，低氧均使去甲肾上腺素和肾上腺素的血浆水平升高。我们发现，在低氧期间，纳洛酮输注会使血浆肾上腺素水平呈剂量依赖性升高。低氧20分钟时，0.1mg/kg纳洛酮剂量组的血浆肾上腺素水平（几何均值5366pg/ml）显著高于单纯低氧组（997pg/ml）。其他剂量的纳洛酮未改变肾上腺素反应。在所研究的任何剂量下，纳洛酮均未增强血浆去甲肾上腺素水平。因此，纳洛酮增强了胎羊对低氧血症的血浆肾上腺素反应，提示阿片肽作为交感肾上腺系统的调节剂发挥作用。本研究中观察到的纳洛酮剂量反应差异表明，这种调节主要是通过对μ受体的拮抗作用实现的。
