# HYPOXIA AND CONTROL OF FETAL BREATHING MOVEMENTS

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 1994 · $169,148

## Abstract

Hypoxia inhibits fetal breathing movements, a central effect which is
mediated by adenosine and is abolished by transection of the posterior
diencephalon. The proposed studies in fetal sheep have three goals; the
first is to localize diencephalic neurons which mediate hypoxic inhibition
of breathing. Electrical stimulation and specific focal destruction of
cells will map diencephalic neurons which depress fetal breathing.
Adenosine A1 receptor antoradiography and microinjections of adenosine
receptor agonists and antagonists will determine the distribution of
adenosine-sensitive cells which trigger hypoxic inhibition. The second
goal is to determine the mechanism by which hypoxia increases brain
adenosine concentrations. Microdialysis with inhibitors of ecto-5'-
nucleotidase and adenosine kinase will be used to measure changes in
central adenosine levels during graded hypoxia. These experiments will
establish whether the hypoxia-induced increase in brain extracellular
adenosine levels is caused by extra- or intracellular degradation of ATP
or by decreased intracellular recycling of adenosine. Thus these studies
will help determine whether an O2-limitation of mitochondrial oxidative
phosphorylation elicits hypoxic inhibition. Because the incidence of fetal
breathing returns to normal during prolonged O2 deficiency (>8h), the
third goal of this study is to evaluate mechanisms by which breathing
might adapt to prolonged hypoxia. Breathing and changes in brain adenosine
concentrations will be assessed during sustained hypoxia, and these
studies will help determine whether a fall in central levels of adenosine
contributes to breathing adaptation. The extent of adenosine receptor
desensitization in the diencephalon will also be assessed in vitro by
agonist competition of [3H]antagonist binding to A1 adenosine receptors
using autoradiographic techniques. These studies will determine whether a
change in A1 receptor coupling to guanine nucleotide-binding proteins
contributes to hypoxic adaptation.  Hypoxic inhibition of fetal breathing
appears to be part of a survival mechanism whereby oxygen that would
otherwise be used for breathing is made available to the fetal heart and
brain; consequently, hypoxic inhibition and the adaptation that occurs
during continued oxygen deficiency have relevance to our understanding of
hypoxia-induced fetal brain injury. Understanding the mechanism by which
hypoxia depresses fetal breathing may also be relevant to infants prone to
sudden death (SIDS), to adults with sleep apnea, and to the general
control of respiration.

## Key facts

- **NIH application ID:** 2197671
- **Project number:** 2R01HD018478-07A2
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **SAM.gov UEI:** RN64EPNH8JC6
- **Principal Investigator:** Brian J. Koos
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1994
- **Award amount:** $169,148
- **Award type:** 2
- **Project period:** 1985-08-01 → 1998-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/2197671

## Citation

> US National Institutes of Health, RePORTER application 2197671, HYPOXIA AND CONTROL OF FETAL BREATHING MOVEMENTS (2R01HD018478-07A2). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/2197671. Licensed CC0.

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