title: Mild chronic hypoxemia modifies expression of brain stem angiotensin peptide receptors and reflex responses in fetal sheep.
abstract: 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 PO(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 x min(-1) x 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.
authors.affiliation: Dept. of Obstetrics and Gynecology, Wake Forest Univ. School of Medicine, Winston Salem, NC 27157, USA. vpulgar@wfubmc.edu
authors.forename: Victor M
authors.initials: VM
authors.lastname: Pulgar
authors.forename: Jason Kyung-soo
authors.initials: JK
authors.lastname: Hong
authors.forename: Jewell A
authors.initials: JA
authors.lastname: Jessup
authors.forename: Angela G
authors.initials: AG
authors.lastname: Massmann
authors.forename: Debra I
authors.initials: DI
authors.lastname: Diz
authors.forename: Jorge P
authors.initials: JP
authors.lastname: Figueroa
mesh_terms: D000804:Angiotensin II / Q000378:metabolism; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D057912:Angiotensin II Type 2 Receptor Blockers; D000818:Animals; D031608:Area Postrema / Q000378:metabolism; D001237:Asphyxia / Q000503:physiopathology; D017704:Baroreflex / Q000502:physiology*; D001784:Blood Gas Analysis; D001794:Blood Pressure / Q000502:physiology; D001933:Brain Stem / Q000378:metabolism / Q000503:physiopathology*; D005260:Female; D005312:Fetal Blood / Q000737:chemistry / Q000378:metabolism; D005333:Fetus / Q000378:metabolism / Q000503:physiopathology*; D015870:Gene Expression / Q000502:physiology*; D006339:Heart Rate / Q000502:physiology; D006454:Hemoglobins / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D000860:Hypoxia / Q000097:blood / Q000378:metabolism / Q000503:physiopathology*; D008297:Male; D008526:Medulla Oblongata / Q000378:metabolism; D009847:Olivary Nucleus / Q000378:metabolism; D011247:Pregnancy; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism; D044139:Receptor, Angiotensin, Type 2 / Q000378:metabolism; D011945:Receptors, Angiotensin / Q000378:metabolism*; D012756:Sheep; D017552:Solitary Nucleus / Q000378:metabolism
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D057912:Angiotensin II Type 2 Receptor Blockers; D006454:Hemoglobins; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin; D000804:Angiotensin II