title: Role of angiotensin II in the pressor response to cortisol in fetal sheep during late gestation.
abstract: 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.
authors.affiliation: Department of Physiology, University of Cambridge, Downing Street, Cambridge CB2 3EG, UK. ajf1005@cam.ac.uk
authors.forename: A J
authors.initials: AJ
authors.lastname: Forhead
authors.forename: A L
authors.initials: AL
authors.lastname: Fowden
mesh_terms: D000804:Angiotensin II / Q000502:physiology*; D000818:Animals; D001572:Benzofurans / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology*; D005260:Female; D005333:Fetus / Q000187:drug effects / Q000502:physiology*; D005865:Gestational Age; D006854:Hydrocortisone / Q000494:pharmacology* / Q000502:physiology; D008297:Male; D044140:Receptor, Angiotensin, Type 1 / Q000502:physiology*; D012756:Sheep
chemical_list: D001572:Benzofurans; D044140:Receptor, Angiotensin, Type 1; D000804:Angiotensin II; C089586:saprisartan potassium; D006854:Hydrocortisone