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.