Cardiac corticosteroid receptors mediate the enlargement of the ovine fetal heart induced by chronic increases in maternal cortisol.
Previous studies have demonstrated that modest, physiologically relevant increases in maternal cortisol in late gestation result in enlargement of the fetal heart. In this study, we investigated the role of mineralocorticoid receptor (MR) or glucocorticoid receptor (GR) in this enlargement. Ewes with single fetuses were randomly assigned at approximately 120 days of gestation to one of four groups: maternal cortisol infusion (1 mg/kg per day, cortisol); maternal cortisol infusion with fetal intrapericardial infusion of the MR antagonist (MRa) potassium canrenoate (600 microg/day; cortisol+MRa); maternal cortisol infusion with fetal intrapericardial infusion of the GR antagonist (GRa) mifepristone (50 microg/day, cortisol+GRa); and maternal saline infusion (control). At approximately 130 days of gestation, fetal heart to body weight ratio and right ventricular (RV) and left ventricular (LV) free wall thicknesses were increased in the cortisol group when compared with control group. Fetal hearts from the cortisol+MRa group weighed significantly less, with thinner LV, RV, and interventricular septum walls, when compared with the cortisol group. Fetal hearts from the cortisol+GRa group had significantly thinner RV walls than the cortisol group. Fetal arterial pressure and heart rate were not different among groups at 130 days. Picrosirius red staining of fetal hearts indicated that the increased size was not accompanied by cardiac fibrosis. These results suggest that physiologic increases in maternal cortisol in late gestation induce fetal cardiac enlargement via MR and, to a lesser extent, by GR, and indicate that the enlargement is not secondary to an increase in fetal blood pressure or an increase in fibrosis within the fetal heart.
Reini
Seth A
SA
Department of Pharmacodynamics, College of Pharmacy, University of Florida, Box 100487, Gainesville, Florida 32610-0487, USA.
Dutta
Garima
G
Wood
Charles E
CE
Keller-Wood
Maureen
M
D000324:Adrenocorticotropic Hormone / Q000097:blood; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002191:Canrenoic Acid / Q000494:pharmacology; D006332:Cardiomegaly / Q000139:chemically induced*; D005260:Female; D005318:Fetal Heart / Q000187:drug effects* / Q000473:pathology; D006854:Hydrocortisone / Q000008:administration & dosage / Q000494:pharmacology*; D007150:Immunohistochemistry; D015735:Mifepristone / Q000494:pharmacology; D000451:Mineralocorticoid Receptor Antagonists / Q000494:pharmacology; D011247:Pregnancy; D011965:Receptors, Glucocorticoid / Q000037:antagonists & inhibitors / Q000378:metabolism; D018161:Receptors, Mineralocorticoid / Q000378:metabolism; D011987:Receptors, Steroid / Q000037:antagonists & inhibitors / Q000378:metabolism*; D012756:Sheep
D000893:Anti-Inflammatory Agents; D000451:Mineralocorticoid Receptor Antagonists; D011965:Receptors, Glucocorticoid; D018161:Receptors, Mineralocorticoid; D011987:Receptors, Steroid; D015735:Mifepristone; D002191:Canrenoic Acid; D000324:Adrenocorticotropic Hormone; D006854:Hydrocortisone