Karamanoukian H L, Glick P L, Wilcox D T, Rossman J E, Azizkhan R G
Buffalo Institute of Fetal Therapy (BIFT), Children's Hospital of Buffalo, University of New York 14222.
J Pediatr Surg. 1995 Jan;30(1):5-9. doi: 10.1016/0022-3468(95)90597-9.
The pathophysiology of congenital diaphragmatic hernia (CDH) results from a combination of pulmonary hypoplasia, pulmonary hypertension, and surfactant deficiency. Previously we demonstrated that inhaled nitric oxide (NO), a known vasodilator, only improves oxygenation and decreases pulmonary artery pressures when the lamb model of CDH is pretreated with exogenous surfactant. Nitric oxide synthase (NOS) in endothelial cells is responsible for the production of NO, a mediator of smooth muscle cell relaxation. Pulmonary hypertension in CDH may result from a defect in the endogenous production of NO. Our aim was to determine whether the main pulmonary artery trunks in CDH lambs have NOS immunoreactivity. Cryostat sections of paraformaldehyde-fixed specimens of pulmonary artery and aortic rings from 10 CDH lambs and five control lambs were processed for NADPH-diaphorase activity. Immunolocalization of NOS was studied in paraformaldehyde-fixed sections and compared with serially cut specimens from identical rings that were tested for NADPH-diaphorase activity. Intense NADPH-diaphorase staining was present in the intimal layer (endothelial lining) of the pulmonary artery and aortic rings of both the CDH and control lambs. This activity colocalized with NOS immunoreactivity in all specimens. Both NOS immunoreactivity and NADPH-diaphorase staining were lacking in cartilage, which were used as negative controls. NOS is present in the main pulmonary artery trunks of CDH lambs. To our knowledge, this is the first report of NOS immunoreactivity in CDH. We can only speculate whether this activity is preserved in other areas of the vascular tree in CDH, ie, pulmonary capillaries and veins. Perhaps the pulmonary hypertension in CDH is not caused by an NOS deficiency.
先天性膈疝（CDH）的病理生理学是由肺发育不全、肺动脉高压和表面活性剂缺乏共同导致的。此前我们证明，吸入一氧化氮（NO）作为一种已知的血管扩张剂，仅在CDH羔羊模型用外源性表面活性剂预处理后，才能改善氧合并降低肺动脉压力。内皮细胞中的一氧化氮合酶（NOS）负责产生NO，它是平滑肌细胞舒张的介质。CDH中的肺动脉高压可能源于内源性NO产生的缺陷。我们的目的是确定CDH羔羊的主要肺动脉干是否具有NOS免疫反应性。对10只CDH羔羊和5只对照羔羊的肺动脉和主动脉环的多聚甲醛固定标本进行冰冻切片，以检测NADPH-黄递酶活性。在多聚甲醛固定切片中研究NOS的免疫定位，并与来自相同环的连续切片标本进行比较，这些标本用于检测NADPH-黄递酶活性。在CDH羔羊和对照羔羊的肺动脉和主动脉环的内膜层（内皮衬里）中均存在强烈的NADPH-黄递酶染色。在所有标本中，这种活性与NOS免疫反应性共定位。软骨中缺乏NOS免疫反应性和NADPH-黄递酶染色，软骨用作阴性对照。NOS存在于CDH羔羊的主要肺动脉干中。据我们所知，这是关于CDH中NOS免疫反应性的首次报道。我们只能推测这种活性在CDH血管树的其他区域，即肺毛细血管和静脉中是否保留。也许CDH中的肺动脉高压不是由NOS缺乏引起的。
