Effect of steroid hormones on blood pressure.
1. There is considerable evidence to support the idea that steroid hormones have the potential to increase blood pressure that may not always be via 'classical' mineralocorticoid or glucocorticoid action. 2. Epidemiological studies, together with the evidence from studies in animals, proposed the link between an adverse intra-uterine environment (i.e. undernutrition or excess exposure to glucocorticoids) and the early onset of cardiovascular and metabolic diseases later in life. 3. We tested this by treating pregnant ewes (and foetuses) with excess steroid early in pregnancy. The mean ages at which the prenatal exposure to glucocorticoid (dexamethasone 0.48 mg/h for 48 h) occurred were 22 +/- 0.4 to 29 +/- 0.4 days (prenatal treatment group 1; PTG1) and 59 +/- 2 to 66 +/- 2 days (PTG2), respectively. Basal blood pressures and hormones and the vascular responsiveness to graded doses of angiotensin II and noradrenaline, or to a 5-day adrenocorticotropin hormone treatment (ACTH), in lambs at 4, 10 and 19 months of age were studied. 4. Basal mean arterial pressure in PTG1 group (80 +/- 1 mmHg at 4 months; 83 +/- 1 mmHg at 10 months; and 89 +/- 1 mmHg at 19 months; n = 6) was significantly different (P < 0.05 in all groups) from that in the control group of lambs (74 +/- 2 mmHg at 4 months; 76 +/- 1 mmHg at 10 months; and 81 +/- 1 mmHg at 19 months; n = 7). Prenatal glucocorticoid exposure did not alter vascular responsiveness to noradrenaline, angiotensin II and ACTH in these sheep at any of the ages studied. 5. These results suggest that foetal exposure to maternal dexamethasone during defined developmental stage or 'window' programmes elevated blood pressure, which persists later in life.
Howard Florey Institute of Experimental Physiology and Medicine, University of Melbourne, Parkville, Australia. m.dodic@hfi.unimelb.edu.au
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Dodic
E M
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Wintour
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Whitworth
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Coghlan
D000324:Adrenocorticotropic Hormone / Q000494:pharmacology; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D003907:Dexamethasone / Q000633:toxicity*; D005260:Female; D005938:Glucocorticoids / Q000633:toxicity*; D006973:Hypertension / Q000209:etiology / Q000503:physiopathology*; D009638:Norepinephrine / Q000494:pharmacology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D012756:Sheep; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D005938:Glucocorticoids; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D003907:Dexamethasone; D000324:Adrenocorticotropic Hormone; D009638:Norepinephrine