Chicoine Louis G, Paffett Michael L, Girton Mark R, Metropoulus Matthew J, Joshi Mandar S, Bauer John Anthony, Nelin Leif D, Resta Thomas C, Walker Benjimen R
Center for Gene Therapy, Columbus Children's Research Institute, The Ohio State University, Columbus, Ohio, Columbus, OH 43205, USA.
Am J Physiol Lung Cell Mol Physiol. 2007 Nov;293(5):L1261-70. doi: 10.1152/ajplung.00235.2006. Epub 2007 Sep 7.
Nitric oxide (NO) is an important regulator of vasomotor tone in the pulmonary circulation. We tested the hypothesis that the role NO plays in regulating vascular tone changes during early postnatal development. Isolated, perfused lungs from 7- and 14-day-old Sprague-Dawley rats were studied. Baseline total pulmonary vascular resistance (PVR) was not different between age groups. The addition of KCl to the perfusate caused a concentration-dependent increase in PVR that did not differ between age groups. However, the nitric oxide synthase (NOS) inhibitor N(omega)-nitro-L-arginine augmented the K(+)-induced increase in PVR in both groups, and the effect was greater in lungs from 14-day-old rats vs. 7-day-old rats. Lung levels of total endothelial, inducible, and neuronal NOS proteins were not different between groups; however, the production rate of exhaled NO was greater in lungs from 14-day-old rats compared with those of 7-day-old rats. Vasodilation to 0.1 microM of the NO donor spermine NONOate was greater in 14-day lungs than in 7-day lungs, and lung levels of both soluble guanylyl cyclase and cGMP were greater at 14 days than at 7 days. Vasodilation to 100 microM of the cGMP analog 8-(4-chlorophenylthio)guanosine-3',5'-cyclic monophosphate was greater in 7-day lungs than in 14-day lungs. Our results demonstrate that the pulmonary vascular bed depends more on NO production to modulate vascular tone at 14 days than at 7 days of age. The observed differences in NO sensitivity may be due to maturational increases in soluble guanylyl cyclase protein levels.
一氧化氮（NO）是肺循环中血管舒缩张力的重要调节因子。我们验证了以下假说：在出生后早期发育过程中，NO在调节血管张力变化方面发挥作用。我们研究了来自7日龄和14日龄Sprague-Dawley大鼠的离体灌注肺。各年龄组之间的基线总肺血管阻力（PVR）无差异。向灌注液中添加氯化钾会导致PVR呈浓度依赖性增加，各年龄组之间无差异。然而，一氧化氮合酶（NOS）抑制剂N（ω）-硝基-L-精氨酸增强了两组中钾离子诱导的PVR增加，且在14日龄大鼠的肺中作用比7日龄大鼠的肺中更大。两组之间总内皮型、诱导型和神经元型NOS蛋白的肺水平无差异；然而，14日龄大鼠肺中呼出NO的产生率高于7日龄大鼠。14日龄肺对0.1微摩尔的NO供体精胺NONOate的血管舒张作用大于7日龄肺，并且14天时可溶性鸟苷酸环化酶和cGMP的肺水平均高于7天。7日龄肺对100微摩尔的cGMP类似物8-（4-氯苯硫基）鸟苷-3'，5'-环一磷酸的血管舒张作用大于14日龄肺。我们的结果表明，与7日龄相比，14日龄时肺血管床在调节血管张力方面更多地依赖于NO的产生。观察到的NO敏感性差异可能是由于可溶性鸟苷酸环化酶蛋白水平的成熟增加所致。
