bq-123 and Fetal-Hypoxia

To study endotoxin induced changes in pulmonary blood flow during normoxia and hypoxia and analyzed the role of nitric oxide (NO) and endothelin (ET) in this process.. Twenty-seven fetal sheep were chronically instrumented at 107+/-1 days (term is 147 days). Experiments were performed 3 days after surgery. Fetuses were randomized into four groups. Group 1: control group (n=5); Group 2: LPS group (n=6) with lipopolysaccharide (LPS) injection at t -60min; Group 3: L-NAME (n=6) with nitro-l-arginine methyl ester (l-NAME) treatment at t -75min; Group 4: l-NAME+LPS group (n=6) with nitro-l-arginine methyl ester (l-NAME) pre-treatment at t -75min and LPS administration at t -60min as described above; Group 5: BQ123+LPS group (n=4) with BQ123 pre-treatment at t -75min and LPS injection at t -60min as described above.. Unlike in control fetuses, there was a marked elevation in pulmonary perfusion in response to LPS induced endotoxemia during normoxia (+112%; p<0.01), which was even further increased during hypoxia (+434%; p<0.001). This increase was partially blocked by BQ123 (p<0.05) and completely abolished by pre-treatment with l-NAME (p<0.001).. During fetal endotoxemia, pulmonary perfusion is increased by LPS induced production of nitric oxide. This may have a significant impact in the fetal inflammatory response syndrome, particularly in the inflammation of the fetal lungs observed in response to intrauterine infection.

Topics: Acid-Base Equilibrium; Animals; Animals, Newborn; Antihypertensive Agents; Blood Pressure; Endothelins; Endotoxemia; Enzyme Inhibitors; Female; Fetal Hypoxia; Fetus; Heart Rate, Fetal; Lipopolysaccharides; Lung; NG-Nitroarginine Methyl Ester; Nitric Oxide; Peptides, Cyclic; Random Allocation; Regional Blood Flow; Sheep