Onset of pulmonary ventilation in fetal sheep produces pial arteriolar constriction dependent on cytochrome p450 ω-hydroxylase activity

Hiroto Ohata, Debebe Gebremedhin, Jayashree Narayanan, David R. Harder, Raymond C. Koehler

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)412-417
Number of pages6
JournalJournal of applied physiology
Volume109
Issue number2
DOIs
StatePublished - Aug 2010

Keywords

  • 20-HETE
  • Cerebral circulation
  • Hyperoxia
  • Neonatal circulation
  • Oxygen sensing
  • Pial artery

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

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