Gozal D, Torres J E, Gozal E, Nuckton T J, Dixon M K, Gozal Y M, Hornby P J
Department of Pediatrics, Tulane University School of Medicine, New Orleans, LA 70112, USA.
Biol Neonate. 1998;73(4):264-74. doi: 10.1159/000013985.
Gasping is an important mechanism for survival. Nitric oxide (NO) plays an excitatory role in brainstem regions mediating respiratory responses to hypoxia. We hypothesized that neural structures mediating anoxia-induced gasping would display NO dependency. Two- to 15-day-old rat pups underwent anoxic exposures with 100% N2 in a plethysmograph following administration of N-nitro-L-arginine methyl ester (L-NAME), a nitric oxide synthase (NOS) blocker, L-arginine (L-Arg), a NO precursor, or normal saline. In general, gasp latencies were significantly shorter after L-Arg, and were prolonged with L-NAME. Furthermore, NOS inhibition prolonged gasping duration and reduced gasping frequency at all postnatal ages, although this effect was particularly increased with advancing postnatal age. NADPH-diaphorase staining and Western blots of protein lysates from the lateral tegmental field, the putative neural center underlying gasp generation, revealed progressively increased neuronal NOS abundance with animal maturation. We conclude that anoxia-induced gasping neurogenesis is modulated by NO mechanisms in neonatal pups. We postulate that higher NO brainstem concentrations may favor early autoresuscitation but be detrimental to overall survival during prolonged asphyxia.
喘息是一种重要的生存机制。一氧化氮（NO）在介导对缺氧的呼吸反应的脑干区域中发挥兴奋作用。我们假设，介导缺氧诱导喘息的神经结构会表现出对NO的依赖性。在给予一氧化氮合酶（NOS）抑制剂N-硝基-L-精氨酸甲酯（L-NAME）、NO前体L-精氨酸（L-Arg）或生理盐水后，将2至15日龄的幼鼠置于体积描记器中，用100%氮气进行缺氧暴露。一般来说，L-Arg给药后喘息潜伏期显著缩短，而L-NAME给药后则延长。此外，NOS抑制在所有出生后年龄阶段均延长了喘息持续时间并降低了喘息频率，尽管随着出生后年龄的增长这种作用尤其增强。对推测为喘息产生基础的神经中枢——外侧被盖区的蛋白质裂解物进行NADPH-黄递酶染色和蛋白质免疫印迹分析，结果显示随着动物成熟，神经元型NOS丰度逐渐增加。我们得出结论，新生幼鼠中缺氧诱导的喘息神经发生受NO机制调节。我们推测，脑干中较高的NO浓度可能有利于早期自动复苏，但对长时间窒息期间的总体生存有害。
