TY - JOUR
T1 - Onset of pulmonary ventilation in fetal sheep produces pial arteriolar constriction dependent on cytochrome p450 ω-hydroxylase activity
AU - Ohata, Hiroto
AU - Gebremedhin, Debebe
AU - Narayanan, Jayashree
AU - Harder, David R.
AU - Koehler, Raymond C.
PY - 2010/8
Y1 - 2010/8
N2 - With the onset of ventilation at birth, cerebral blood flow decreases as oxygenation increases, but the mechanism of cerebral vasoconstriction is unknown. Cytochrome P-450 ω-hydroxylase activity metabolizes arachidonic acid to 20-HETE, a potent vasoconstrictor, in a physiologically relevant O 2-dependent manner. We tested the hypothesis that the ω-hydroxylase inhibitor, 17-octadecynoic acid (17-ODYA), reduces cerebral vasoconstriction during in utero ventilation with O2 in fetal sheep. In anesthetized pregnant sheep near term, the fetal head was exposed with the rest of the body remaining in utero. Pial arteriolar diameter was measured by intravital microscopy through a closed cranial window superfused with vehicle or 17-ODYA. Mechanical ventilation of the fetal lungs with a high O2 mixture to increase arterial PO2 from ∼20 to ∼90 Torr markedly decreased pial arteriolar diameter by 24 ± 3% (±SE) without a change in arterial pressure. In contrast, superfusion of 17-ODYA completely blocked the decrease in diameter (2 ± 3%) with increased oxygenation. Vasoconstriction to hypocapnia was intact after returning to the baseline intrauterine oxygenation state, thereby indicating that the effect of 17-ODYA was selective for increased oxygenation. In cerebral arteries isolated from fetal sheep, increasing oxygenation increased 20-HETE production. We conclude that cytochrome P-450 ω-hydroxylase activity makes an important contribution to cerebral vasoconstriction associated with the onset of ventilation at birth.
AB - With the onset of ventilation at birth, cerebral blood flow decreases as oxygenation increases, but the mechanism of cerebral vasoconstriction is unknown. Cytochrome P-450 ω-hydroxylase activity metabolizes arachidonic acid to 20-HETE, a potent vasoconstrictor, in a physiologically relevant O 2-dependent manner. We tested the hypothesis that the ω-hydroxylase inhibitor, 17-octadecynoic acid (17-ODYA), reduces cerebral vasoconstriction during in utero ventilation with O2 in fetal sheep. In anesthetized pregnant sheep near term, the fetal head was exposed with the rest of the body remaining in utero. Pial arteriolar diameter was measured by intravital microscopy through a closed cranial window superfused with vehicle or 17-ODYA. Mechanical ventilation of the fetal lungs with a high O2 mixture to increase arterial PO2 from ∼20 to ∼90 Torr markedly decreased pial arteriolar diameter by 24 ± 3% (±SE) without a change in arterial pressure. In contrast, superfusion of 17-ODYA completely blocked the decrease in diameter (2 ± 3%) with increased oxygenation. Vasoconstriction to hypocapnia was intact after returning to the baseline intrauterine oxygenation state, thereby indicating that the effect of 17-ODYA was selective for increased oxygenation. In cerebral arteries isolated from fetal sheep, increasing oxygenation increased 20-HETE production. We conclude that cytochrome P-450 ω-hydroxylase activity makes an important contribution to cerebral vasoconstriction associated with the onset of ventilation at birth.
KW - 20-HETE
KW - Cerebral circulation
KW - Hyperoxia
KW - Neonatal circulation
KW - Oxygen sensing
KW - Pial artery
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U2 - 10.1152/japplphysiol.01090.2009
DO - 10.1152/japplphysiol.01090.2009
M3 - Article
C2 - 20489034
AN - SCOPUS:77955616253
VL - 109
SP - 412
EP - 417
JO - Journal of Applied Physiology
JF - Journal of Applied Physiology
SN - 0161-7567
IS - 2
ER -