Mild chronic hypoxemia modifies expression of brain stem angiotensin peptide receptors and reflex responses in fetal sheep

Departments of 1 Obstetrics and Gynecology and 2 Surgical Sciences, Wake Forest University School of Medicine, Winston-Salem, North Carolina Submitted 14 January 2009 ; accepted in final form 3 June 2009 The effects of chronic mild hypoxemia on the binding of angiotensin receptors in selected brain...

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Published in:American journal of physiology. Regulatory, integrative and comparative physiology integrative and comparative physiology, 2009-08, Vol.297 (2), p.R446-R452
Main Authors: Pulgar, Victor M, Hong, Jason Kyung-soo, Jessup, Jewell A, Massmann, Angela G, Diz, Debra I, Figueroa, Jorge P
Format: Article
Language:English
Subjects:
ACE inhibitors
Angiotensin II - metabolism
Angiotensin II Type 1 Receptor Blockers - pharmacology
Angiotensin II Type 2 Receptor Blockers
Animals
Area Postrema - metabolism
Asphyxia - physiopathology
Baroreflex - physiology
Binding sites
Blood Gas Analysis
Blood Pressure - physiology
Brain
Brain Stem - metabolism
Brain Stem - physiopathology
Cardiovascular system
Effects
Female
Fetal Blood - chemistry
Fetal Blood - metabolism
Fetus - metabolism
Fetus - physiopathology
Gene Expression - physiology
Heart Rate - physiology
Hemoglobins - metabolism
Hydrogen-Ion Concentration
Hypoxia - blood
Hypoxia - metabolism
Hypoxia - physiopathology
Male
Medulla Oblongata - metabolism
Olivary Nucleus - metabolism
Peptides
Pregnancy
Receptor, Angiotensin, Type 1 - metabolism
Receptor, Angiotensin, Type 2 - metabolism
Receptors, Angiotensin - metabolism
Sheep
Solitary Nucleus - metabolism
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Summary:Departments of 1 Obstetrics and Gynecology and 2 Surgical Sciences, Wake Forest University School of Medicine, Winston-Salem, North Carolina Submitted 14 January 2009 ; accepted in final form 3 June 2009 The effects of chronic mild hypoxemia on the binding of angiotensin receptors in selected brain stem nuclei and reflex responses were studied in fetal sheep. Fetal and maternal catheters were placed at 120 days' gestation, and animals received intratracheal maternal administration of nitrogen ( n = 16) or compressed air in controls ( n = 19). Nitrogen infusion was adjusted to reduce fetal brachial artery P O 2 by 25% during 5 days. Spontaneous baroreflex sensitivity and spectral analysis of the pulse interval were analyzed during the 5 days hypoxemia period using 90 min of daily recording. Brains of control and hypoxemic animals were collected, and brain stem angiotensin receptor binding was studied by in vitro autoradiography at 130 days of gestation. After 5 days of hypoxemia, some animals in each group were submitted to one complete umbilical cord occlusion during 5 min. [ 125 I]sarthran binding showed that chronic mild hypoxemia significantly increases angiotensin type 1 receptor, angiotensin type 2 receptor, and ANG-(1-7) angiotensin receptor binding sites in the nucleus tractus solitarius and dorsal motor nucleus of the vagus ( P < 0.05). Hypoxemia induced lower baroreflex sensitivity and a higher low frequency-to-high frequency ratio in the fetus, consistent with a shift from vagal to sympathetic autonomic cardiac regulation. Cord occlusion to elicit a chemoreflex response induced a greater bradycardic response in hypoxemic fetuses (slope of the initial fall in heart rate; 11.3 ± 1.9 vs. 6.4 ± 1.2 beats·min –1 ·s –1 , P < 0.05). In summary, chronic mild hypoxemia increased binding of angiotensin receptors in brain stem nuclei, decreased spontaneous baroreflex gain, and increased chemoreflex responses to asphyxia in the fetus. These results suggest hypoxemia-induced alterations in brain stem mechanisms for cardiovascular control. fetus; hypoxemia; baroreflex Address for reprint requests and other correspondence: V. M. Pulgar, Dept. of Obstetrics and Gynecology, Wake Forest Univ. School of Medicine, Winston Salem, NC 27157 (e-mail: vpulgar{at}wfubmc.edu )
ISSN:0363-6119
1522-1490
DOI:10.1152/ajpregu.00023.2009