Role of angiotensin II in the pressor response to cortisol in fetal sheep during late gestation

Glucocorticoids increase blood pressure in utero , but the mechanisms responsible are unclear. This study investigated the hypothesis that the hypertensive effects of cortisol depend upon a functional renin–angiotensin system (RAS). The study examined, in the sheep fetus, whether blockade of the Ang II type 1 (AT 1 ) specific receptor prevented the cortisol‐induced increase in blood pressure. From 124 ± 1 days of gestation (term 145 ± 2 days), 27 chronically catheterized sheep fetuses were infused i.v. for 5 days with one of the following: (1) saline (0.9% NaCl at 2.5 ml day −1 , n = 6); (2) cortisol (3−5 mg kg −1 day −1 , n = 7); (3) AT 1 receptor antagonist (GR138950, 1–3 mg kg −1 day −1 in saline, GRS, n = 7); or (4) cortisol and GR138950 (GRC, n = 7). On all days of infusion, plasma cortisol was greater in both groups of cortisol‐treated fetuses than in the respective control fetuses ( P < 0.05), and GR138950 prevented the pressor response to exogenous Ang II. Over 5 days of infusion, blood pressure increased by a maximum of 7.6 ± 1.4 mmHg (mean ± s.e.m. , P < 0.05) in the cortisol‐, but not saline‐infused, fetuses. Blockade of the AT 1 receptor caused significant reductions in blood pressure in both GRS‐ and GRC‐treated groups ( P < 0.05); in the GRS‐treated fetuses, the fall in blood pressure was significant from the first day of infusion, while in GRC‐treated fetuses the decrement was not significant until the second day ( P < 0.05). Over the period of the infusion, decreases in arterial blood pH andP a ,O   2, and an increase inP a ,CO   2, were observed in the fetuses treated with the AT 1 receptor antagonist ( P < 0.05). Therefore, in the sheep fetus, 5 days of AT 1 receptor antagonism suppresses the cortisol‐induced rise in blood pressure. These results suggest that cortisol may increase blood pressure within 24 h of administration by a mechanism that is independent of the fetal RAS. Thereafter, Ang II, via the AT 1 receptor, may mediate, in part, the hypertensive effects of cortisol in utero .