Role of prostanoids in the regulation of cerebral blood flow during normoxia and hypoxia in the fetal sheep.
The fetal cardiovascular responses to hypoxia include decreased peripheral blood flow and increased cerebral, cardiac, and adrenal blood flow. Prostanoids, metabolites of cyclooxygenase enzyme activity, have potent effects on vascular tone in both the adult and the fetus. To examine the role of prostanoids in the regulation of fetal cerebral blood flow (CBF) during acute hypoxic stress, eight near term fetal sheep were studied after infusing vehicle or diclofenac, a cyclooxygenase inhibitor, followed by a 30-min period of hypoxia (arterial Po(2) 12 Torr). In the control experiments, CBF, measured continuously with laser Doppler flowmetry, increased to 148% of baseline values (p < 0.01) and cerebral vascular resistance decreased to 70% of baseline values after 30 min of hypoxic stress. During diclofenac infusion, hypoxia resulted in a CBF increase to only 129% of baseline, a significant attenuation (p < 0.05), accompanied by decreased plasma prostanoid concentrations. Increases in mean arterial blood pressure during hypoxia were also attenuated by diclofenac infusion. Flow and pressure responses were not accompanied by changes in cerebral vascular resistance. These results indicate that prostanoids indirectly modulate fetal CBF responses to hypoxia, but that their effects are mediated through modulation of systemic rather than cerebral vascular tone.
Nishida
Naoko
N
Department of Obstetrics and Gynecology, Nippon Medical School, Tokyo, Japan 13-8602.
Blood
Arlin B
AB
Hunter
Christian J
CJ
Bragg
Shannon
S
Williams
James
J
Pearce
William J
WJ
Power
Gordon G
GG
D000818:Animals; D001794:Blood Pressure; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D051545:Cyclooxygenase 1 / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D004008:Diclofenac / Q000494:pharmacology*; D005260:Female; D005333:Fetus / Q000033:anatomy & histology / Q000502:physiology*; D006339:Heart Rate; D000860:Hypoxia / Q000378:metabolism*; D020768:Middle Cerebral Artery / Q000201:enzymology; D011247:Pregnancy; D011453:Prostaglandins / Q000378:metabolism*; D011897:Random Allocation; D012039:Regional Blood Flow / Q000187:drug effects*; D012756:Sheep
D016861:Cyclooxygenase Inhibitors; D011453:Prostaglandins; D004008:Diclofenac; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2