Angiotensin II infusion in vivo does not modulate cortisol secretion in the late-gestation ovine fetus.

Abstract

Maturation of the fetal adrenal gland is critical for the onset of ovine parturition. It has long been proposed that the fetal adrenal gland may be under inhibitory influences during late gestation. In vitro evidence has suggested that angiotensin II may be such an inhibitory factor and may help to prevent a premature increase in cortisol concentrations. The aim of this study was to test the effect of angiotensin II infusion in vivo on basal cortisol concentrations and fetal adrenal responsiveness to an ACTH-(1-24) challenge. Fetuses received a continuous infusion of either angiotensin II (100 ng . min-1 . kg-1; n = 7) or saline (2 ml/h; n = 4), which commenced at 140 days of gestation (GA) and continued for a total of 50 h. Adrenal responsiveness to the administration of ACTH-(1-24) (5 microg/kg) was determined during angiotensin II or saline infusions at both 2 and 48 h after infusion onset. Angiotensin II had no significant effect on adrenal responsiveness after acute (2 h) or chronic (48 h) infusion. There was no effect of saline or angiotensin II infusion on basal immunoreactive ACTH or cortisol concentrations after 2 h, but there was a significant increase in basal cortisol concentrations in both treatment groups by 48 h, probably reflecting the normal rise in cortisol concentrations at this GA. Mean arterial blood pressure was significantly increased in angiotensin II-infused fetuses only. This study has therefore found no evidence to suggest that angiotensin II infusion in vivo modulates fetal basal cortisol concentrations or adrenal responsiveness in the last week of gestation, in contrast with previous in vitro studies. These results throw into question the proposed role of angiotensin II as a negative modulator of adrenal function in the ovine fetus.