Conahey George R, Power Gordon G, Hopper Andrew O, Terry Michael H, Kirby Laura S, Blood Arlin B
Center for Perinatal Biology, Department of Pediatrics, Loma Linda University, Loma Linda, California 92354, USA.
Pediatr Res. 2008 Oct;64(4):375-80. doi: 10.1203/PDR.0b013e318180f08b.
Inhaled nitric oxide (iNO) has many extrapulmonary effects. As the half-life of nitric oxide (NO) in blood is orders of magnitude less than the circulation time from lungs to the brain, the mediator of systemic effects of iNO is unknown. We hypothesized that concentrations of nitrite, a circulating byproduct of NO with demonstrated NO bioactivity, would increase in blood and cerebrospinal fluid (CSF) during iNO therapy. iNO (80 ppm) was given to six newborn lambs and results compared with six control lambs. Blood and CSF nitrite concentrations increased 2-fold in response to iNO. cGMP increased in blood but not CSF suggesting brain guanylate cyclase activity was not increased. When sodium nitrite was infused i.v. blood and CSF nitrite levels increased within 10 min and reached similar levels of 14.6 +/- 1.5 microM after 40 min. The reactivity of nitrite in Hb-free brain homogenates was investigated, with the findings that nitrite did not disappear nor did measurable amounts of s-nitroso, n-nitroso, or iron-nitrosyl-species appear. We conclude that although nitrite diffuses freely between blood and CSF, due to its lack of reactivity in the brain, nitrite's putative role as the mediator of the systemic effects of iNO is limited to intravascular reactions.
吸入一氧化氮（iNO）具有多种肺外效应。由于一氧化氮（NO）在血液中的半衰期比从肺到脑的循环时间短几个数量级，iNO全身效应的介质尚不清楚。我们假设，亚硝酸盐作为具有已证实的NO生物活性的NO循环副产物，其在血液和脑脊液（CSF）中的浓度在iNO治疗期间会增加。对六只新生羔羊给予iNO（80 ppm），并将结果与六只对照羔羊进行比较。作为对iNO的反应，血液和脑脊液中的亚硝酸盐浓度增加了两倍。血液中的cGMP增加，但脑脊液中未增加，这表明脑鸟苷酸环化酶活性未增加。静脉输注亚硝酸钠时，血液和脑脊液中的亚硝酸盐水平在10分钟内升高，40分钟后达到相似的水平，即14.6±1.5微摩尔。研究了无血红蛋白脑匀浆中亚硝酸盐的反应性，结果发现亚硝酸盐没有消失，也没有出现可测量量的亚硝基硫醇、亚硝基化合物或铁亚硝基化合物。我们得出结论，虽然亚硝酸盐可在血液和脑脊液之间自由扩散，但由于其在脑中缺乏反应性，亚硝酸盐作为iNO全身效应介质的假定作用仅限于血管内反应。
