Haemodynamic characteristics of hypertension induced by prenatal cortisol exposure in sheep

Karen Margaret Moritz, Miodrag Dodic, Andrew John Jefferies, Marelyn Wintour-Coghlan, Robert Mark De Matteo, Reetu Ragni Singh, Roger George Evans

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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 hemodynamic 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 26-28 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 adrenergic receptor blockade (intravenous infusion of 0.15 mg kg(-1)h(-1) phentolamine plus 0.4 mg kg(-1)h(-1) 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, while cardiac output tended to be 8 less in cortisol-exposed than 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-exposed than 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 at least partly dependent on an increased influence of sympathetic vasomotor drive. Taken together with previous findings our observations suggest that prenatal cortisol and dexamethasone program altered adult cardiovascular function via distinct mechanistic pathways.
Original languageEnglish
Pages (from-to)981 - 987
Number of pages7
JournalClinical and Experimental Pharmacology and Physiology
Issue number10
Publication statusPublished - 2009

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