Haemodynamic characteristics of hypertension induced by prenatal cortisol exposure in sheep.
1. Administration of glucocorticoids to ewes early in pregnancy results in offspring with hypertension in adulthood. The hypertension in female offspring exposed to dexamethasone is associated with increased cardiac output, but whether this is also true in cortisol-exposed offspring is unknown. 2. Systemic haemodynamic variables were measured under basal conditions in castrated male and female adult sheep exposed to cortisol (5 mg/h) or saline (0.19 mL/h) from 26 to 28 days of gestation. To examine the contribution of the autonomic nervous system to maintenance of basal arterial pressure in established hypertension in cortisol-exposed sheep, responses to adrenoceptor blockade (intravenous infusion of 0.15 mg/kg per h phentolamine plus 0.4 mg/kg per h propranolol) and ganglionic blockade (intravenous infusion of 125 mg/h hexamethonium) were examined in castrated male offspring. 3. Mean arterial pressure and calculated systemic vascular resistance were 9% and 17% greater, whereas cardiac output tended to be 8% less, in cortisol-compared with saline-exposed sheep. These effects were not sex dependent. The depressor response to ganglionic blockade and the initial phase of the depressor response to adrenoceptor blockade were greater in cortisol-compared with saline-exposed sheep. 4. These results indicate that hypertension in offspring exposed prenatally to cortisol is associated with increased total peripheral resistance, mimicking observations in human patients with chronic hypertension. Furthermore, the increased vascular resistance appears to be dependent, at least in part, on an increased effect of sympathetic vasomotor drive. Taken together with previous findings, the present observations suggest that prenatal cortisol and dexamethasone programme altered adult cardiovascular function via distinct mechanistic pathways.
Moritz
Karen M
KM
Department of Anatomy and Developmental Biology, Monash University, Clayton 3800, Australia. k.moritz@uq.edu.au
Dodic
Miodrag
M
Jefferies
Andrew J
AJ
Wintour
E Marelyn
EM
DeMatteo
Robert
R
Singh
Reetu R
RR
Evans
Roger G
RG
D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage; D005260:Female; D006439:Hemodynamics / Q000187:drug effects*; D018738:Hexamethonium / Q000008:administration & dosage; D006854:Hydrocortisone; D006973:Hypertension / Q000139:chemically induced* / Q000517:prevention & control; D007262:Infusions, Intravenous; D008297:Male; D018811:Maternal Exposure / Q000009:adverse effects; D010646:Phentolamine / Q000008:administration & dosage; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000503:physiopathology*; D011433:Propranolol / Q000008:administration & dosage; D012756:Sheep; D054928:Validation Studies as Topic
D000959:Antihypertensive Agents; D018738:Hexamethonium; D011433:Propranolol; D006854:Hydrocortisone; D010646:Phentolamine