title: The role of nitric oxide on fetal cardiovascular control during normoxia and acute hypoxia in 0.75 gestation sheep.
abstract: OBJECTIVE
  The role of nitric oxide in control of fetal cardiovascular functions and of cerebral blood flow during normoxia and acute hypoxia is only partially known. We studied the effects of nitric oxide synthase inhibition on the distribution of cardiac output in preterm sheep using N(omega)-nitro-L-arginine methyl ester (L-NAME).
  
  
  METHODS
  Thirteen fetal sheep were instrumented at a gestational age of 107 days. Three days later fetuses received L-NAME (n = 7) or vehicle infusion (n = 6). At 0 minutes, acute hypoxia was induced by occlusion of the maternal aorta for 2 minutes. Organ blood flows (microsphere method) and physiologic variables (fetal heart rate, mean arterial pressure [MAP], oxygen saturation, and pH) were measured at -75, -1, +2, +4, and +30 minutes.
  
  
  RESULTS
  L-NAME caused bradycardia and an increase in MAP. A significant decrease in cardiac output by 32% occurred in the control group during the control period, which was consequently reflected in organ blood flows. L-NAME injection reduced cardiac output by 64% during normoxia. Blood flow to the fetal body, placenta, and cerebrum decreased by 62%, 66%, and 55%, respectively. During acute hypoxia, L-NAME did not change the redistribution of cardiac output toward the central organs. In the L-NAME group MAP increased, and fetal heart rate was maintained; in contrast, in controls MAP initially decreased and then returned to control values while fetal heart rate decreased. After hypoxia L-NAME delayed the recovery of cardiac output and blunted the increase in blood flow to the brain and heart.
  
  
  CONCLUSIONS
  Although influenced by fetal stress after extensive instrumentation, the results of this study indicate that nitric oxide plays a role in fetal cardiovascular control during normoxia and acute hypoxia. Nitric oxide also mediates the increase in blood flow to the brain and heart immediately after hypoxia.
authors.affiliation: Department of Obstetrics and Gynecology, University of Maastricht, Maastricht, The Netherlands.
authors.forename: A B C
authors.initials: AB
authors.lastname: Coumans
authors.forename: Y
authors.initials: Y
authors.lastname: Garnier
authors.forename: S
authors.initials: S
authors.lastname: Supçun
authors.forename: A
authors.initials: A
authors.lastname: Jensen
authors.forename: T H M
authors.initials: TH
authors.lastname: Hasaart
authors.forename: R
authors.initials: R
authors.lastname: Berger
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002245:Carbon Dioxide / Q000097:blood; D002302:Cardiac Output / Q000187:drug effects; D002319:Cardiovascular System / Q000196:embryology* / Q000503:physiopathology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005312:Fetal Blood / Q000737:chemistry; D005318:Fetal Heart / Q000187:drug effects / Q000503:physiopathology; D005311:Fetal Hypoxia / Q000503:physiopathology*; D005865:Gestational Age; D006340:Heart Rate, Fetal; D006863:Hydrogen-Ion Concentration; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D010100:Oxygen / Q000097:blood; D010920:Placenta / Q000098:blood supply; D011247:Pregnancy; D012039:Regional Blood Flow; D012756:Sheep
chemical_list: D004791:Enzyme Inhibitors; D002245:Carbon Dioxide; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D010100:Oxygen; D019331:NG-Nitroarginine Methyl Ester