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

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 NMDA 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 NMDA 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 NMDA receptor antagonist, dizocipline (1 mg), was injected ICV. At time 4h, the dose of dizocipline was repeated, together with angiotensin II (AngII, 6.5 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 swallous/min; P < .001). ICV AngII 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 of aCSF did not change fetal swallowing activity (1.0 ± 0.1 swallows/min), while ICV AngII resulted in a significant increase inf etal 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 AngII-stimulated fetal swallowing. We speculate that reduced NMDA receptor expression within the forebrain dispogenic neurons may account for observed differences in drinking activities between the fetus/neonate and the adult.

Keywords

Amniotic fluid volume fetal swallowing glutamate-NMDA receptors

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