MATURATION-RELATED CHANGES IN ENDOTHELIAL NITRIC-OXIDE SYNTHASE IMMUNOLOCALIZATION IN DEVELOPING OVINE LUNG

It is unknown whether high fetal pulmonary vascular tone is due in par t to absent or decreased endothelial nitric oxide synthase (eNOS), the enzyme that produces nitric oxide in the vascular endothelium. To det ermine the timing of appearance and maturational changes of eNOS in th e developing pulmonary circulation, we performed immunohistochemistry in lungs from fetal, neonatal, and adult sheep. Using a mouse monoclon al antibody against bovine aortic eNOS, we found immunoreactive eNOS s electively in the endothelium and it was present at all fetal ages. Im munoreactivity was seen as early as 29% gestation in the developing ca pillaries coursing through fetal mesenchyme. By 6 days after birth, im munoreactivity was decreased in most vessels and nearly absent in the distal pulmonary arteries of adult animals. We conclude that immunorea ctive eNOS is present very early in fetal life and appears to decrease postnatally. We speculate that the early presence of eNOS in the feta l lung supports a possible role for endogenous nitric oxide activity i n the regulation of vascular tone or angiogenesis in the developing pu lmonary circulation.