Hardy P, Peri K G, Lahaie I, Varma D R, Chemtob S
Department of Pediatrics, University of Montréal, Québec, Canada.
Circ Res. 1996 Sep;79(3):504-11. doi: 10.1161/01.res.79.3.504.
We tested the hypothesis that hyperoxia does not cause adequate constriction of choroidal vessels of the newborn (1 to 5 days old) pig, resulting in increased O2 delivery to the retina, possibly due to excess production and/or effects of vasodilators such as nitric oxide (NO). Hyperoxia (100% O2, 45 minutes) led to a decrease in retinal blood flow (RBF) of both newborn and juvenile (5 to 6 weeks old) pigs and also reduced choroidal blood flow (ChBF) in juvenile but not in newborn pigs; the absence of hyperoxia-induced ChBF response in the newborn was associated with a rise in choroidal O2 delivery. Ibuprofen (prostaglandin G/H synthase inhibitor) and 1,3-dimethyl-2-thiourea (a free radical scavenger) did not modify the choroidal hemodynamic responses to hyperoxia in newborn pigs. However, in newborn animals treated with the NO synthase (NOS) inhibitor NG-nitro-L-arginine methyl ester (L-NAME), hyperoxia caused a decrease in blood flow and O2 delivery to the choroid. Consistent with these effects of L-NAME, hyperoxia induced an increase in choroidal cGMP in newborn pigs ventilated with 100% O2 and stimulated nitrite production in isolated choroids exposed to hyperoxia from newborn but not juvenile pigs; these effects were inhibited by NOS blockers. Also, both constitutive and inducible NOS activities were higher in choroidal tissues from newborn than from juvenile animals. In addition, the vasorelaxant effect of the NO donor sodium nitroprusside in vitro was also greater on choroids from newborn than from juvenile pigs. Finally, L-NAME prevented the hyperoxia-induced increase in peroxidation products in the choroid of newborns. It is concluded that hyperoxia does not lead to a decrease in blood flow and O2 delivery to the choroid of the newborn because of increased NO synthesis and effects; since the choroid is the main source of O2 supply to the retina, the present data contribute in providing an explanation for the increased susceptibility of the immature neonate to hyperoxia-induced retinopathy.
高氧不会引起新生（1至5日龄）仔猪脉络膜血管充分收缩，从而导致视网膜的氧气输送增加，这可能是由于血管舒张剂如一氧化氮（NO）的过量产生和/或作用。高氧（100%氧气，45分钟）导致新生仔猪和幼年（5至6周龄）仔猪的视网膜血流量（RBF）均减少，并且使幼年仔猪的脉络膜血流量（ChBF）降低，但新生仔猪的脉络膜血流量未受影响；新生仔猪缺乏高氧诱导的脉络膜血流量反应与脉络膜氧气输送增加有关。布洛芬（前列腺素G/H合酶抑制剂）和1,3 - 二甲基 - 2 - 硫脲（一种自由基清除剂）并未改变新生仔猪脉络膜对高氧的血流动力学反应。然而，在用一氧化氮合酶（NOS）抑制剂NG - 硝基 - L - 精氨酸甲酯（L - NAME）处理的新生动物中，高氧导致脉络膜血流量和氧气输送减少。与L - NAME的这些作用一致，高氧诱导用100%氧气通气的新生仔猪脉络膜中环鸟苷酸（cGMP）增加，并刺激新生但非幼年仔猪分离的脉络膜在高氧环境下产生亚硝酸盐；这些作用被NOS阻滞剂抑制。此外，新生动物脉络膜组织中的组成型和诱导型NOS活性均高于幼年动物。另外，体外NO供体硝普钠对新生仔猪脉络膜的血管舒张作用也大于幼年仔猪。最后，L - NAME阻止了高氧诱导的新生仔猪脉络膜中过氧化产物的增加。得出的结论是，由于NO合成和作用增加，高氧不会导致新生仔猪脉络膜的血流量和氧气输送减少；由于脉络膜是视网膜氧气供应的主要来源，目前的数据有助于解释未成熟新生儿对高氧诱导的视网膜病变易感性增加的原因。
