title: The role of the adrenal medulla and peripheral sympathetic nerves in the physiological responses of the fetal sheep to hypoxia.
abstract: In studies on the role of the peripheral sympathetic system during fetal life the effects of adrenal demedullation or chemical sympathectomy on the responses of the fetal sheep to hypoxaemia have been studied. Fetal sheep of 127-138 days gestation were either adrenal demedullated by injection of acid formalin into the adrenal medulla, chemically sympathectomised by chronic treatment with guanethidine sulphate, or subjected to both manipulations. None of these treatments had any effect upon resting heart rate and blood pressure, or blood gas status. Hypoxia was induced by giving the pregnant ewe 9% O2 and 3% CO2 in N2 to breathe for 60 min. This depressed fetal PO2 by about 30% in the intact and all but the adrenal-demedullated, chemically-sympathectomised fetuses, where the fall was about 50%. Similarly in this group of fetuses there was a sharp fall in plasma pH contrasting with little change in the other fetuses. Adrenal demedullation blocked completely the hypoxia-induced rise in fetal plasma adrenaline, and reduced that of noradrenaline to 10% of normal, implying that during hypoxia most of the plasma elevation of catecholamines is of adrenal origin. In contrast, and possibly to compensate for the blunted catecholamine response, plasma AVP increases during hypoxia were substantially enhanced by adrenal demedullation. Fetal hypoxia was associated normally with a fall in heart rate and rise in blood pressure. Adrenal demedullation had no effect on the heart rate changes, thought to be a reflex response to rise in blood pressure, but abolished the rise in blood pressure during hypoxia. Chemical sympathectomy, in contrast, abolished the fall in heart rate even though blood pressure rose. This shows clearly that reflex changes in heart rate during hypoxia can be uncoupled from those in blood pressure. Turning to the endocrine effects of demullation, cortisol and ACTH responses to hypoxia were much increased, whilst those of insulin were depressed. During chemical sympathectomy these responses were much accentuated in the case of cortisol and ACTH but depressed for insulin. A feature of these effects was that the endocrine changes in the adrenal-demedullated fetuses, whilst initially high, were not sustained for the 60 min of hypoxia. The same was true of the fetal matabolic responses to hypoxia reflected in plasma glucose, lactate and non-esterified fatty acids. Most of the results in this study are consistent with the proposal that in the fetus adrenal catecholamines are important in sustaining responses to hypoxia, but not normally initiating them.
authors.affiliation: Nuffield Institute for Medical Research, University of Oxford, U.K.
authors.forename: C T
authors.initials: CT
authors.lastname: Jones
authors.forename: M M
authors.initials: MM
authors.lastname: Roebuck
authors.forename: D W
authors.initials: DW
authors.lastname: Walker
authors.forename: B M
authors.initials: BM
authors.lastname: Johnston
mesh_terms: D000313:Adrenal Medulla / Q000502:physiology*; D000324:Adrenocorticotropic Hormone / Q000097:blood; D000818:Animals; D001784:Blood Gas Analysis; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure; D002395:Catecholamines / Q000097:blood; D005314:Embryonic and Fetal Development; D005230:Fatty Acids, Nonesterified / Q000097:blood; D006339:Heart Rate; D006854:Hydrocortisone / Q000097:blood; D006863:Hydrogen-Ion Concentration; D000860:Hypoxia / Q000097:blood / Q000503:physiopathology*; D007328:Insulin / Q000097:blood; D007773:Lactates / Q000097:blood; D019344:Lactic Acid; D010525:Peripheral Nerves / Q000502:physiology*; D012756:Sheep; D013564:Sympathetic Nervous System / Q000502:physiology*; D014667:Vasopressins / Q000097:blood
chemical_list: D001786:Blood Glucose; D002395:Catecholamines; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D007773:Lactates; D014667:Vasopressins; D019344:Lactic Acid; D000324:Adrenocorticotropic Hormone; D006854:Hydrocortisone