Effect of cortisol on blood pressure and the renin-angiotensin system in fetal sheep during late gestation.
The effects of cortisol on blood pressure and the circulating components of the renin-angiotensin system (RAS) were investigated in sheep fetuses during late gestation and after exogenous cortisol infusion. Plasma cortisol concentration was greater in fetuses at 140 +/- 1 days of gestation (term 145 +/- 2 days) compared to those studied earlier in gestation (128 +/- 1 days), although, because of wide inter-animal variation, no differences were observed in blood pressure or plasma angiotensin II (AII), renin or angiotensinogen (Ao) concentrations. At 129 +/- 1 days of gestation, an infusion of cortisol for 5 days (2-3 mg kg(-1) day(-1) i.v.) increased plasma cortisol concentration to a value normally seen close to term. This rise in plasma cortisol was accompanied by increases in blood pressure and plasma concentrations of AII, renin and Ao. When observations from all fetuses were considered, plasma cortisol concentration correlated with plasma AII and renin, and blood pressure correlated with plasma cortisol and AII concentrations. Intravenous administration of an AII type 1 (AT(1))-specific receptor antagonist (3 mg kg(-1) GR138950) caused a reduction in blood pressure in all fetuses; the hypotensive response was greatest in fetuses studied near term and in the cortisol-treated fetuses. Overall, the magnitude of the hypotension induced by GR138950, and the concomitant rise in plasma renin, both correlated with the plasma cortisol concentration before GR138950 treatment. These findings show that, in the sheep fetus during late gestation, the RAS becomes more important in the maintenance of resting blood pressure when plasma cortisol concentration is elevated, whether endogenously or exogenously.
Forhead
A J
AJ
Department of Physiology, University of Cambridge, Downing Street, Cambridge CB2 3EG, UK.ajf1005@cam.ac.uk
Broughton Pipkin
F
F
Fowden
A L
AL
D000804:Angiotensin II / Q000097:blood; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage; D001572:Benzofurans / Q000008:administration & dosage; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology*; D004334:Drug Administration Schedule; D005333:Fetus / Q000378:metabolism; D005865:Gestational Age; D006854:Hydrocortisone / Q000008:administration & dosage / Q000097:blood*; D007262:Infusions, Intravenous; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D012083:Renin / Q000097:blood; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000502:physiology*; D012756:Sheep / Q000196:embryology* / Q000378:metabolism*
D057911:Angiotensin Receptor Antagonists; D000959:Antihypertensive Agents; D001572:Benzofurans; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D000804:Angiotensin II; D012083:Renin; C089586:saprisartan potassium; D006854:Hydrocortisone