title: Effects of low dose dexamethasone treatment on basal cardiovascular and endocrine function in fetal sheep during late gestation.
abstract: This study investigated the effects on ovine fetal basal cardiovascular and endocrine functions of fetal intravenous dexamethasone treatment, resulting in circulating concentrations that were one-fifth of the values measured clinically in human infants following maternal antenatal glucocorticoid therapy. Between 117-120 days gestation (dGA; term: ca 145 dGA), 26 Welsh Mountain sheep fetuses were surgically prepared under general anaesthesia with vascular catheters and a Transonic flow probe positioned around a femoral artery. At 125 +/- 1 dGA, fetuses were infused with dexamethasone (2.06 +/- 0.13 microg kg(-1) h(-1) i.v.; n = 13) or saline (n = 13) for 48 h. Daily fetal arterial blood samples were taken and cardiovascular data were recorded continuously (data acquisition system). Pressor, vasoconstrictor and chronotropic responses to exogenously administered doses of phenylephrine, angiotensin II and arginine vasopressin (AVP) were determined at 124 +/- 1 (pre-infusion), 126 +/- 1 (during infusion) and 128 +/- 1 (post-infusion) dGA. Fetal cardiac baroreflex curves were constructed using peak pressor and heart rate responses to phenylephrine. Dexamethasone treatment elevated fetal mean arterial blood pressure by 8.1 +/- 1.0 mmHg (P < 0.05), increased femoral vascular resistance by 0.65 +/- 0.12 mmHg (ml min(-1))(-1) (P < 0.05), depressed plasma noradrenaline concentrations and produced a shift in set-point, but not sensitivity, of the cardiac baroreflex (P < 0.05). Elevations in fetal arterial blood pressure, but not femoral vascular resistance and the shift in baroreflex set-point, persisted at 48 h following dexamethasone treatment. By 48 h following dexamethasone infusion, basal plasma noradrenaline concentration was restored, whilst plasma adrenaline and neuropeptide Y (NPY) concentrations were enhanced, compared with controls (P < 0.05). Fetal dexamethasone treatment did not alter the fetal pressor or femoral vasoconstrictor responses to adrenergic, vasopressinergic or angiotensinergic agonists. These data show that fetal treatment with low concentrations of dexamethasone modifies fetal basal cardiovascular and endocrine functions. Depending on the variable measured, these changes may reverse, persist or become enhanced by 48 h following the cessation of treatment.
authors.affiliation: Department of Physiology, University of Cambridge, Cambridge CB2 3EG, UK.
authors.forename: Andrew J W
authors.initials: AJ
authors.lastname: Fletcher
authors.forename: Hugh H G
authors.initials: HH
authors.lastname: McGarrigle
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: D000818:Animals; D001127:Arginine Vasopressin / Q000097:blood; D017704:Baroreflex / Q000187:drug effects; D001784:Blood Gas Analysis; D001794:Blood Pressure / Q000187:drug effects; D002395:Catecholamines / Q000097:blood; D003907:Dexamethasone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004702:Endocrine Glands / Q000187:drug effects*; D005260:Female; D005333:Fetus / Q000187:drug effects / Q000502:physiology*; D005865:Gestational Age; D006340:Heart Rate, Fetal / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D006728:Hormones / Q000097:blood; D009478:Neuropeptide Y / Q000097:blood; D011247:Pregnancy; D012039:Regional Blood Flow / Q000187:drug effects; D014655:Vascular Resistance / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects
chemical_list: D002395:Catecholamines; D006728:Hormones; D009478:Neuropeptide Y; D001127:Arginine Vasopressin; D003907:Dexamethasone