title: Cardiovascular and endocrine responses to acute hypoxaemia during and following dexamethasone infusion in the ovine fetus.
abstract: This study investigated the effects of fetal treatment with dexamethasone on ovine fetal cardiovascular defence responses to acute hypoxaemia, occurring either during or 48 h following the period of glucocorticoid exposure. To address the mechanisms underlying these responses, chemoreflex function and plasma concentrations of catecholamines, neuropeptide Y (NPY) and vasopressin were measured. Under general halothane anaesthesia, 26 Welsh Mountain sheep fetuses were surgically prepared for long-term recording at between 117 and 120 days of gestation (dGA; term is approximately 145 days) with vascular catheters and a Transonic flow probe around a femoral artery. Following at least 5 days of recovery, fetuses were randomly assigned to one of two experimental groups. After 48 h of baseline recording, at 125 +/- 1 dGA, half of the fetuses (n = 13) were continuously infused I.V. with dexamethasone for 48 h at a rate of 2.06 +/- 0.13 microg kg-1 h-1. The remaining 13 fetuses were infused with heparinized saline at the same rate (controls). At 127 +/- 1 dGA, 2 days from the onset of infusions, seven fetuses from each group were subjected to 1 h of acute hypoxaemia. At 129 +/- 1 dGA, 2 days after the end of infusions, six fetuses from each group were subjected to 1 h of acute hypoxaemia. Similar reductions in fetal partial pressure of arterial oxygen occurred in control and dexamethasone-treated fetuses during the acute hypoxaemia protocols. In control fetuses, acute hypoxaemia led to transient bradycardia, femoral vasoconstriction and significant increases in plasma concentrations of catecholamines, vasopressin and NPY. In fetuses subjected to acute hypoxaemia during dexamethasone treatment, the increase in plasma NPY was enhanced, the bradycardic response was prolonged, and the plasma catecholamine and vasopressin responses were diminished. In fetuses subjected to acute hypoxaemia 48 h following dexamethasone treatment, femoral vasoconstriction and plasma catecholamine and vasopressin responses were enhanced, whilst the prolonged bradycardia and augmented plasma NPY responses persisted. These data show that fetal treatment with dexamethasone modifies the pattern and magnitude of fetal cardiovascular responses to acute oxygen deprivation. Modifications to different mechanisms mediating the fetal defence responses to acute hypoxaemia that occur during dexamethasone treatment may reverse, persist or even become enhanced by 48 h following the treatment period.
authors.affiliation: Department of Physiology, University of Cambridge, Downing Street, UK.
authors.forename: Andrew J W
authors.initials: AJ
authors.lastname: Fletcher
authors.forename: David S
authors.initials: DS
authors.lastname: Gardner
authors.forename: C Mark B
authors.initials: CM
authors.lastname: Edwards
authors.forename: Abigail L
authors.initials: AL
authors.lastname: Fowden
authors.forename: Dino A
authors.initials: DA
authors.lastname: Giussani
mesh_terms: D000136:Acid-Base Equilibrium / Q000502:physiology; D000208:Acute Disease; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D002245:Carbon Dioxide / Q000097:blood; D002395:Catecholamines / Q000097:blood; D002628:Chemoreceptor Cells / Q000502:physiology; D003907:Dexamethasone / Q000494:pharmacology*; D004703:Endocrine System / Q000187:drug effects* / Q000502:physiology; D005260:Female; D005333:Fetus / Q000187:drug effects / Q000502:physiology; D005938:Glucocorticoids / Q000494:pharmacology*; D006340:Heart Rate, Fetal / Q000187:drug effects* / Q000502:physiology; D000860:Hypoxia / Q000188:drug therapy* / Q000503:physiopathology*; D009478:Neuropeptide Y / Q000097:blood; D010100:Oxygen / Q000097:blood; D011247:Pregnancy; D012039:Regional Blood Flow / Q000187:drug effects / Q000502:physiology; D012756:Sheep; D014655:Vascular Resistance / Q000187:drug effects / Q000502:physiology; D014667:Vasopressins / Q000097:blood
chemical_list: D002395:Catecholamines; D005938:Glucocorticoids; D009478:Neuropeptide Y; D014667:Vasopressins; D002245:Carbon Dioxide; D003907:Dexamethasone; D010100:Oxygen