VENTILATION AND OXYGENATION INDUCE ENDOTHELIAL NITRIC-OXIDE SYNTHASE GENE-EXPRESSION IN THE LUNGS OF FETAL LAMBS

At birth, ventilation and oxygenation immediately decrease pulmonary v ascular resistance (PVR) and increase pulmonary blood flow (PBF); more gradual changes occur over the next several hours. Nitric oxide, prod uced by endothelial nitric oxide synthase (eNOS), mediates these gradu al changes. To determine how ventilation and oxygenation affect eNOS g ene expression, 12 fetal lambs were ventilated for 8 h without changin g fetal descending aortic blood gases or pH (rhythmic distension) or w ith 100% oxygen (O-2 ventilation). Vascular pressures and PBF were mea sured. Total RNA, protein, and tissue sections were prepared from lung tissue for RNase protection assays, Western blotting, and in situ hyb ridization, O-2 ventilation increased PBF and decreased PVR more than rhythmic distension (P < 0.05). Rhythmic distension increased eNOS mRN A expression; O-2 ventilation increased eNOS mRNA expression more and increased eNOS protein expression (P < 0.05). To define the mechanisms responsible for these changes, ovine fetal pulmonary arterial endothe lial cells were exposed to 1, 21, or 95% O-2 or to shear stress, 95% O -2 increased eNOS mRNA and protein expression (P < 0.05), Shear stress increased eNOS mRNA and protein expression (P < 0.05). Increased oxyg enation but more importantly increased PBF with increased shear stress induce eNOS gene expression and contribute to pulmonary vasodilation after birth.