Exposure of newborn rats to
hyperoxia impairs alveolarization.
Nitric oxide (NO) may prevent this evolution. Angiogenesis and factors involved in this process, but also other
growth factors (GFs) involved in alveolar development, are likely potential therapeutic targets for NO. We studied the effects of the NO donor, [Z]-1-[N-(2-aminoethyl)-N-(2-ammonioethyl)aminio]diazen-1-ium-1, 2-diolate, also termed
DETANONOate (D-NO), on
hyperoxia-induced changes in key regulatory factors of alveolar development in neonatal rats, and its possible preventive effect on the physiologic consequences of
hyperoxia. Newborn rat pups were randomized at birth to
hyperoxia (> 95% O2) or room air exposure for 6 or 10 d, while receiving D-NO or its diluent. On Day 6, several GFs and their receptors were studied at pre- and/or post-translational levels.
Elastin transcript determination on Day 6, and
elastin deposition in tissue and morphometric analysis of the lungs on Day 10, were also performed.
Hyperoxia decreased the expression of
vascular endothelial growth factor (
VEGF) receptor (VEGFR) 2,
fibroblast growth factor (FGF)-18, and
FGF receptors (FGFRs) FGFR3 and FGFR4, increased mortality, and impaired alveolarization and capillary growth. D-NO treatment of
hyperoxia-exposed pups restored the expression level of FGF18 and FGFR4, induced an increase of both
VEGF mRNA and
protein, enhanced
elastin expression, and partially restored
elastin deposition in alveolar walls. Although, under the present conditions, D-NO failed to prevent the physiologic consequences of
hyperoxia in terms of survival and lung alveolarization, our findings demonstrate molecular effects of NO on GFs involved in alveolar development that may have contributed to the protective effects previously reported for NO.