Maternal glucocorticoid treatment programs alterations in the renin-angiotensin system of the ovine fetal kidney.
Ovine fetuses exposed to high concentrations of synthetic (dexamethasone, D) or naturally occurring glucocorticoids (cortisol, F) in utero during early gestation develop high blood pressure in adulthood. To investigate potential mechanisms involved, we examined the role of the renal renin-angiotensin system (RAS). Ewes were infused with isotonic saline (S, n = 11), D (n = 12, 0.48 mg/h), or F (n = 5, 5 mg/h) for 48 h between d 26 and 28 of gestation (term = 150 d). Ewes carrying twins (S, n = 5; D, n = 6; F, n = 5) were killed at 130 d of gestation. The mRNA levels for angiotensinogen, the AT(1) receptor and AT(2) receptor, were increased in the fetal kidneys after D treatment. Prenatal infusions of F produced similar effects on the AT(1) receptor. Single fetuses (S, n = 6; D, n = 6) were cannulated and infused with angiotensin II for 3 d beginning at 127 d of gestation. Basal blood pressure was similar in both groups and increased similarly with angiotensin II infusion. However, increases in urine flow and glomerular filtration rate were significantly reduced and kidney weights increased in the D-treated group. These results indicate that treatment with D very early in gestation causes significant alterations in the RAS in the fetal kidney 100 d later with functional consequences. Changes in the RAS in the developing kidney may be an important mechanism in the development of adult disease.
Moritz
K M
KM
Howard Florey Institute of Experimental Physiology and Medicine, University of Melbourne, Parkville, Victoria 3010, Australia. k.moritz@hfi.unimelb.edu.au
Johnson
K
K
Douglas-Denton
R
R
Wintour
E M
EM
Dodic
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M
D000804:Angiotensin II / Q000008:administration & dosage; D000808:Angiotensinogen / Q000235:genetics; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D015153:Blotting, Western; D003907:Dexamethasone / Q000008:administration & dosage / Q000009:adverse effects; D004231:Diuresis / Q000187:drug effects; D005260:Female; D005865:Gestational Age; D005919:Glomerular Filtration Rate / Q000187:drug effects; D005938:Glucocorticoids / Q000008:administration & dosage / Q000009:adverse effects*; D006854:Hydrocortisone / Q000008:administration & dosage / Q000009:adverse effects; D006973:Hypertension / Q000139:chemically induced; D007150:Immunohistochemistry; D007668:Kidney / Q000196:embryology* / Q000502:physiology; D008431:Maternal-Fetal Exchange; D009693:Nucleic Acid Hybridization; D009929:Organ Size / Q000187:drug effects; D016133:Polymerase Chain Reaction; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D012333:RNA, Messenger / Q000032:analysis; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin / Q000235:genetics; D012084:Renin-Angiotensin System / Q000187:drug effects*; D012756:Sheep
D005938:Glucocorticoids; D012333:RNA, Messenger; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin; D000808:Angiotensinogen; D000804:Angiotensin II; D003907:Dexamethasone; D006854:Hydrocortisone