title: Perinatal regulation of the cerebral circulation: role of nitric oxide and prostaglandins.
abstract: Nitric oxide (NO) influences cerebral vascular tone both in the normal fetus and in the hypoxemic fetus, but during postnatal life this regulating role of NO seems less prominent. It is therefore possible that under conditions when arterial oxygen content is at postnatal levels NO exerts no action on smooth muscle. We therefore examined the impact of NO on cerebral blood flow and vascular resistance in five near-term lamb fetuses during intrauterine ventilation and oxygenation. Four additional fetuses were pretreated with indomethacin to investigate a possible additional regulatory role of prostaglandins on cerebral vascular resistance. Cerebral blood flow (Qbrain) was measured using radionuclide-labeled microspheres. A tracheal tube was inserted to ventilate the fetus. After recovery, Qbrain and resistance in the cerebral vascular bed (Rcer) were measured during the following subsequent conditions: before and after increasing fetal arterial O2 content by ventilation with air, after inhibition of NO production with N(omega)-nitro-L-arginine during and after cessation of ventilation, and finally after infusion of L-arginine to increase nitric oxide production. Ventilation decreased Qbrain (95 +/- 18 to 47 +/- 15 mL/100 g/min) and increased Rcer. N(omega)-Nitro-L-arginine did not alter Qbrain (52 +/- 13 mL/100 g/min) or Rcer during ventilation and oxygenation, indicating no modulating role of NO during higher arterial oxygen content. On cessation of ventilation, PO2 returned to fetal levels and Qbrain increased significantly, but did not return to baseline fetal values (83 +/- 7 mL/min). Infusion of L-arginine increased Qbrain to baseline fetal levels (116 +/- 30 mL/min). However, indomethacin pretreatment prevented the rise in cerebral blood flow after cessation of ventilation and after additional L-arginine infusion (Qbrain 53 +/- 20 and 52 +/- 4 mL/100 g/min. respectively). These studies indicate that, during postnatal levels of arterial oxygen content, NO does not exert an action on smooth muscle cells of the cerebral resistance vessels as it does at lower arterial (fetal) oxygen content. They further show that prostaglandins are important in facilitating the full expression of NO-induced vasodilation.
authors.affiliation: Cardiovascular Research Institute and Department of Pediatrics, Physiology, and Obstetrics, Gynecology and Reproductive Sciences, University of California at San Francisco, 94143, USA.
authors.forename: F
authors.initials: F
authors.lastname: van Bel
authors.forename: A
authors.initials: A
authors.lastname: Sola
authors.forename: C
authors.initials: C
authors.lastname: Roman
authors.forename: A M
authors.initials: AM
authors.lastname: Rudolph
mesh_terms: D000818:Animals; D001120:Arginine / Q000008:administration & dosage / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D001921:Brain / Q000098:blood supply / Q000187:drug effects; D002245:Carbon Dioxide / Q000032:analysis / Q000097:blood; D002339:Carotid Arteries / Q000502:physiology; D002560:Cerebrovascular Circulation / Q000187:drug effects* / Q000502:physiology; D016861:Cyclooxygenase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D005260:Female; D005333:Fetus / Q000187:drug effects / Q000502:physiology; D005865:Gestational Age; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D007213:Indomethacin / Q000008:administration & dosage / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism / Q000494:pharmacology; D010100:Oxygen / Q000032:analysis / Q000097:blood; D010313:Partial Pressure; D011247:Pregnancy; D011453:Prostaglandins / Q000494:pharmacology; D012039:Regional Blood Flow; D012756:Sheep / Q000196:embryology*; D014655:Vascular Resistance / Q000187:drug effects / Q000502:physiology
chemical_list: D016861:Cyclooxygenase Inhibitors; D011453:Prostaglandins; D002245:Carbon Dioxide; D009569:Nitric Oxide; D001120:Arginine; D010100:Oxygen; D007213:Indomethacin