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 ϭ 16) or compressed air in controls (n ϭ 19). Nitrogen infusion was adjusted to reduce fetal brachial artery PO2 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 Ͻ 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 Ϯ 1.9 vs. 6.4 Ϯ 1.2 beats ⅐ min Ϫ1 ⅐ s Ϫ1 , P Ͻ 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 OXYGEN DEPRIVATION IMPOSES diverse challenges to fetal development, with changes in the autonomic cardiovascular control via baroreflex and chemoreflex pathways playing a major role as a survival strategy (16). In fetal sheep, acute episodes of hypoxemia induce a redistribution of cardiac output to maintain blood flow and oxygen delivery to the heart and brain (14). This response is initiated by stimulation of peripheral chemoreceptors and maintained by endocrine mechanisms involving secretion of hormones such as catecholamines, neuropeptide Y, arginine vasopressin, and cortisol (11). During acute severe hypoxia, i.e., complete occlusion of the umbilical cord, fetuses respond with a fall in heart rate (FHR) and an increase in blood pressure. This acute FHR during hypoxia represents a key fetal adaptation, believed to help reduce myocardial work and oxygen requirements (11). This initial bradycardia, which is mediated by chemoreflex vagal pathways (5, 17, 23), occurs before the increase in blood pressure and is an indication of the severity of the hypoxic insult (5). Recently, it was reported that the slope of the initial bradycardia increases during short ...

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