An early prenatal exposure to excess glucocorticoid leads to hypertensive offspring in sheep.
1. Recent studies in animals have linked fetal exposure to excess maternal glucocorticoids with the later occurrence of cardiovascular disorders, particularly hypertension. 2. To test the hypothesis that prenatal treatment could impact on adult blood pressure two groups of pregnant ewes were transported from the farm to the Institute at either 22-29 days of pregnancy (pretreatment group 1) or 59-66 days of pregnancy (pretreatment group 2), subjected to 48 h treatment with dexamethasone (0.28 mg day-1 kg-1 for 2 days) and then returned to the farm. The control group remained at the farm for the entire pregnancy. Lambs were then studied at approximately 4, 10 and 19 months after birth. 3. The basal mean arterial pressure in pretreatment group 1 (80 +/- 1 mmHg at 124 days; 83 +/- 1 mmHg at 309 days and 89 +/- 1 mmHg at 558 days; n = 6) was significantly different (P < 0.05 in all groups) from that in the control group of lambs (74 +/- 2 mmHg at 110 days; 76 +/- 1 mmHg at 323 days and 81 +/- 1 mmHg at 568 days; n = 7). However, prenatal glucocorticoid exposure did not alter vascular sensitivity to noradrenaline, angiotensin II and adrenocorticotropic hormone in these sheep at any of the ages studied, nor did it affect basal or adrenocorticotropic hormone-induced concentrations of cortisol or basal plasma renin concentrations in the lambs at any age. 4. These data support the hypothesis that excess glucocorticoid exposure in early pregnancy, during a critical developmental stage or 'window', programmes higher blood pressure that persists in later life.
Dodic
M
M
Howard Florey Institute of Experimental Physiology and Medicine, University of Melbourne, Parkville, Australia.
May
C N
CN
Wintour
E M
EM
Coghlan
J P
JP
D000324:Adrenocorticotropic Hormone / Q000494:pharmacology; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D003907:Dexamethasone / Q000009:adverse effects*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005865:Gestational Age; D005938:Glucocorticoids / Q000009:adverse effects*; D006854:Hydrocortisone / Q000097:blood; D006973:Hypertension / Q000097:blood / Q000209:etiology*; D009638:Norepinephrine / Q000494:pharmacology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D012756:Sheep
D005938:Glucocorticoids; D000804:Angiotensin II; D003907:Dexamethasone; D000324:Adrenocorticotropic Hormone; D006854:Hydrocortisone; D009638:Norepinephrine