Long-term hypoxia alters ovine fetal endocrine and physiological responses to hypotension

1 Departments of Physiology/Pharmacology and 2 Pediatrics, School of Medicine, Center for Perinatal Biology, Loma Linda University, Loma Linda, California 92350 Submitted 8 December 2003 ; accepted in final form 8 March 2004 Exposure to long-term hypoxia (LTH) results in altered cortisol responses i...

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Published in:American journal of physiology. Regulatory, integrative and comparative physiology integrative and comparative physiology, 2004-07, Vol.287 (1), p.R209-R217
Main Authors: Adachi, Keiichi, Umezaki, Hikaru, Kaushal, Kanchan M, Ducsay, Charles A
Format: Article
Language:English
Subjects:
Adrenocorticotropic Hormone - blood
Animals
Blood Gas Analysis
Blood Pressure - physiology
Endocrine System - physiopathology
Feedback - physiology
Female
Fetus - physiology
Gestational Age
Heart Rate, Fetal - physiology
Hemodynamics - physiology
Hydrocortisone - blood
Hypotension - physiopathology
Hypoxia - physiopathology
Pregnancy
Sheep
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Summary:1 Departments of Physiology/Pharmacology and 2 Pediatrics, School of Medicine, Center for Perinatal Biology, Loma Linda University, Loma Linda, California 92350 Submitted 8 December 2003 ; accepted in final form 8 March 2004 Exposure to long-term hypoxia (LTH) results in altered cortisol responses in the ovine fetus. The present study was designed to test the hypothesis that LTH alters adrenal responsiveness to fetal hypotension. Pregnant ewes were maintained at high altitude (3,820 meters) from day 30 of gestation. Normoxic control and LTH fetuses were catheterized on day 132 of gestation. In the LTH group, maternal P O 2 was maintained comparable to that observed at altitude ( 60 mmHg) by nitrogen infusion through a tracheal catheter. On day 137 , fetuses received a 5-h saline infusion followed by infusion of sodium nitroprusside to reduce fetal arterial pressure by 30–35% for 10 min. The study was repeated on day 139 of gestation with a continuous cortisol infusion (10 µg/min). Hypothalamic and pituitary tissues were collected from additional fetuses for assessment of glucocorticoid receptors. During the saline infusion in response to hypotension, plasma ACTH increased over preinfusion mean values in both groups ( P < 0.05). Plasma cortisol concentrations increased in both groups concomitant with increased ACTH secretion. However, peak values in the LTH fetuses were significantly higher compared with controls ( P < 0.05). During the cortisol infusion, the ACTH response was eliminated in both groups, with ACTH levels significantly lower in the LTH group ( P < 0.05). Glucocorticoid receptor binding was not different between groups. These results demonstrate an enhanced cortisol response to hypotension in LTH fetuses that does not appear to be the result of an increase in negative feedback sensitivity of the hypothalamic-pituitary-adrenal axis. adrenocorticotropin hormone; cortisol; nitroprusside Address for reprint requests and other correspondence: C. A. Ducsay, Center for Perinatal Biology, School of Medicine, Loma Linda Univ., Loma Linda, California 92350 (E-mail: cducsay{at}som.llu.edu ).
ISSN:0363-6119
1522-1490
DOI:10.1152/ajpregu.00701.2003