NO modulates fetoplacental blood flow distribution and whole body oxygen extraction in fetal sheep

It is unknown if nitric oxide (NO) influences the relative level of the left (LV) and right ventricular (RV) outputs, the blood flow distribution between the body and placenta, or whole body O2 extraction and O2 consumption in the fetus. To address these questions eight fetal lambs were chronically instrumented at 128-134 days gestation (term 147 days), and blood flows were measured with radioactive microspheres 3-4 days later at baseline and after inhibition of NO synthesis with N omega-nitro-L-arginine (L-NNA, 10 and 25 mg/kg i.v.). L-NNA progressively reduced the combined ventricular output (P < 0.005) but did not alter the relative levels of the LV and RV outputs. Fetal body blood flow fell by 31% after 10 mg/kg L-NNA (P < 0.005), but a reduction in placental blood flow (P < 0.005) was smaller (20%) and not observed until 25 mg/kg L-NNA. Whole body O2 extraction increased by 71% after 10 mg/kg L-NNA (P < 0.005) and did change further at 25 mg/kg L-NNA, whereas whole body O2 consumption rose by 15% at 10 mg/kg L-NNA (P < 0.05) and returned to baseline at 25 mg/kg L-NNA. These results suggest that, as well as reducing the combined ventricular output, inhibition of fetal NO synthesis redistributes systemic blood flow toward the placenta and increases fetal body O2 extraction. The latter initially increases whole body O2 consumption and then maintains it at near baseline levels after a fall in placental perfusion.