Fetal cerebral and peripheral circulatory responses to hypoxia after nitric oxide synthase inhibition

Andrew P. Harris, Sabah Helou, Christine A. Gleason, Richard J. Traystman, Raymond C. Koehler

Research output: Contribution to journalArticle

Abstract

The increase in cerebral blood flow (CBF) during hypoxia in fetal sheep at 0.6 gestation is less than the increase at 0.9 gestation when normalized for differences in baseline CBF and oxygen consumption. Nitric oxide (NO) synthase (NOS) catalytic activity increases threefold during this period of development. We tested the hypothesis that administration of the NOS inhibitor Nω-nitro-L-arginine methyl ester (L-NAME) decreases the CBF response to systemic hypoxia selectively at 0.9 gestation. We also tested whether any peripheral vasoconstriction during hypoxia is potentiated by L-NAME at 0.9 gestation. Administration of L-NAME increased arterial blood pressure and decreased microsphere-determined CBF during normoxia in fetal sheep at both 0.6 and 0.9 gestation. With subsequent reduction of arterial oxygen content by ∼50%, the percent increase in forebrain CBF in a control group (57 ± 11%; ± SE) and L-NAME-treated group (51 ± 6%) was similar at 0.6 gestation. Likewise, at 0.9 gestation, the increase in CBF was similar in control (90 ± 25%) and L-NAME (80 ± 28%) groups. At 0.9 gestation, L-NAME treatment attenuated the increase in coronary blood flow and increased gastrointestinal vascular resistance during hypoxia. We conclude that NO exerts a basal vasodilatory influence in brain as early as 0.6 gestation in fetal sheep but is not an important mechanism for hypoxic vasodilation in brain at either 0.6 or 0.9 gestation. Thus the developmental increase in NOS catalytic capacity does not appear to be responsible for developmental increases in the CBF response to hypoxia during this period. In contrast, NO modulates the vascular response to hypoxia in heart and gastrointestinal tract.

Original languageEnglish (US)
Pages (from-to)R381-R390
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Volume281
Issue number2 50-2
StatePublished - Aug 29 2001

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Keywords

  • Cerebral blood flow
  • Coronary blood flow
  • Fetus
  • Gastrointestinal blood flow
  • Sheep

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

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