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N-Methyl-D-Aspartate Glutamate Receptor Mediates Spontaneous and Angiotensin II—Stimulated Ovine Fetal Swallowing

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Abstract

Background

In adult rats, N-methyl-D-aspartate (NMDA) receptors have been implicated in the central control of body fluid homeostasis, as intracerebroventricular (ICV) injection of NMD A receptor antagonists suppresses stimulated drinking behavior. Fetal swallowing occurs at a significantly higher rate as compared to adult drinking, contributing to amniotic fluid volume regulation and fetal gastrointestinal development. The aim of present study was to determine the role of central NMD A receptors in the modulation of fetal swallowing activity.

Methods

Eight time-dated pregnant ewes and fetuses were chronically prepared with fetal vascular and ICV catheters, electrocorticogram (ECoG), and esophageal electromyogram electrodes and studied at 130 ± 1 days’ gestation. Following an initial 2-hour baseline period (time 2h), the NMD A receptor antagonist, dizocipline (1 mg), was injected ICV. At time 4h, the dose of dizocipline was repeated, together with angiotensin II (Angll, 6.4 μg). Fetal swallowing was monitored for 2 hours after each injection. Four of these fetuses also received an identical control study (on an alternate day) in which dizocipline was replaced with artificial cerebrospinal fluid (aCSF).

Results

ICV dizocipline injection nearly abolished spontaneous fetal swallowing activities (0.6 ± 0.1 to 0.2 ±0.1 swallows/min; P < .001). ICV Angll in the presence of dizocipline did not demonstrate a dipsogenic effect on fetal swallowing (0.1 ± 0.1; P <.001). In the control study, ICV injection ofaCSF did not change fetal swallowing activity (1.0 ± 0.1 swallows/min), while ICV Angll resulted in a significant increase in fetal swallowing (2.0 ±0.1 swallows/min; P < .001).

Conclusions

This study demonstrates that central NMDA-glutamate receptor-mediated activity contributes to the high rate of spontaneous and Angll-stimulated fetal swallowing. We speculate that reduced NMDA receptor expression within the forebrain dipsogenic neurons may account for observed differences in drinking activities between the fetus/neonate and the adult.

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Authors and Affiliations

  1. Perinatal Research Laboratories, Harbor/UCLA Medical Center, UCLA School of Medicine, Los Angeles, California, USA

    Mostafa A. El-Haddad MD, Conrad R. Chao MD & Michael G. Ross MD, MPH

Authors
  1. Mostafa A. El-Haddad MD
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  2. Conrad R. Chao MD
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  3. Michael G. Ross MD, MPH
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Corresponding author

Correspondence to Michael G. Ross MD, MPH.

Additional information

Mostafa A. El-Haddad is deceased.

Supported by Grants No. ROl DK43311 (M.G.R.) and K08 HD 40251-02 (M.A.E.) from the National Institutes of Health and the March of Dimes.

The authors thank Linda Day for her technical assistance during these studies.

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El-Haddad, M.A., Chao, C.R. & Ross, M.G. N-Methyl-D-Aspartate Glutamate Receptor Mediates Spontaneous and Angiotensin II—Stimulated Ovine Fetal Swallowing. Reprod. Sci. 12, 504–509 (2005). https://doi.org/10.1016/j.jsgi.2005.06.003

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