Inhaled nitric oxide enhances distal lung growth after exposure to hyperoxia in neonatal rats

Yuh Jyh Lin, Neil E. Markham, Vivek Balasubramaniam, Jen Ruey Tang, Anne Maxey, John P. Kinsella, Steven H. Abman

研究成果: Article同行評審

162 引文 斯高帕斯(Scopus)


Exposure of newborn rats to hyperoxia impairs alveolarization and vessel growth, causing abnormal lung structure that persists during infancy. Recent studies have shown that impaired angiogenesis due to inhibition of vascular endothelial growth factor (VEGF) signaling decreases alveolar and vessel growth in the developing lung, and that nitric oxide (NO) mediates VEGF-dependent angiogenesis. The purpose of this study was to determine whether hyperoxia causes sustained reduction of lung VEGF, VEGF receptor, or endothelial NO synthase (eNOS) expression during recovery, and whether inhaled NO improves lung structure in infant rats after neonatal exposure to hyperoxia. Newborn rat pups were randomized to hyperoxia [fraction of inspired oxygen (Fio2), 1.00] or room air exposure for 6 d, and then placed in room air with or without inhaled NO (10 ppm) for 2 wk. Rats were then killed for studies, which included measurements of body weight, lung weight, right ventricular hypertrophy (RVH), morphometric analysis of alveolarization (by mean linear intercept (MLI), radial alveolar counts (RAC), and vascular volume (Vv), and immunostaining and Western blot analysis. In comparison with controls, neonatal hyperoxia reduced body weight, increased MLI, and reduced RAC in infant rats. Lung VEGF, VEGFR-2, and eNOS protein expression were reduced after hyperoxia. Inhaled NO treatment after hyperoxia increased body weight and improved distal lung growth, as demonstrated by increased RAC and Vv and decreased MLI. We conclude that neonatal hyperoxia reduced lung VEGF expression, which persisted during recovery in room air, and that inhaled NO restored distal lung growth in infant rats after neonatal hyperoxia.

頁(從 - 到)22-29
期刊Pediatric Research
出版狀態Published - 2005 7月

All Science Journal Classification (ASJC) codes

  • 兒科、圍產兒和兒童健康


深入研究「Inhaled nitric oxide enhances distal lung growth after exposure to hyperoxia in neonatal rats」主題。共同形成了獨特的指紋。