Maternal hypertension and progeny blood pressure: role of aldosterone and 11beta-HSD.
Epidemiological and experimental evidence suggests that gestational events modulate the level of blood pressure that will be "normal" for the individual as an adult. Glucocorticoid excess during gestation is associated with low birth weight, a large placenta, and adult hypertension in humans and animals. It has been proposed that the deficiency in placental 11beta-hydroxysteroid dehydrogenase activity in humans produces a gestational hormonal milieu, notwithstanding normal circulating levels of glucocorticoids, that predisposes the adult progeny to hypertension. Animal studies indicate that maternal hypertension, excess glucocorticoids, and hydroxysteroid dehydrogenase inhibition program adult blood pressure. Blood pressures of Sprague-Dawley rat dams were manipulated during gestation with continuous intracerebroventricular infusions of vehicle, aldosterone, 11alpha-hydroxyprogesterone, or carbenoxolone at doses known to produce hypertension with no renal effects or with subcutaneous infusions of larger, equally hypertensinogenic doses that produce systemic effects. Blood pressures of all treated dams were significantly greater (P<0.01) during gestation than those of the vehicle ICV control rats but not significantly different from each other. The blood pressures of both male and female progeny (n>/=6 per group, comprising representatives from at least 4 litters) were measured after 6 weeks of age. No significant difference was found in the blood pressure of the pups regardless of the maternal gestational blood pressure or treatment with an enzyme inhibitor, even after high-salt diet challenge.
Gomez-Sanchez
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Research Service, Harry S. Truman Memorial Veterans Hospital, Division of Endocrinology, Diabetes and Metabolism, Department of Internal Medicine, University of Missouri-Columbia, Columbia, MO, USA.
Gomez-Sanchez
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D042842:11-beta-Hydroxysteroid Dehydrogenases; D000328:Adult; D000450:Aldosterone / Q000008:administration & dosage / Q000494:pharmacology / Q000502:physiology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000235:genetics* / Q000502:physiology; D002552:Cerebral Ventricles / Q000187:drug effects / Q000502:physiology; D005260:Female; D018392:Genomic Imprinting; D005865:Gestational Age; D006801:Humans; D006908:Hydroxyprogesterones / Q000008:administration & dosage / Q000494:pharmacology; D006913:Hydroxysteroid Dehydrogenases / Q000378:metabolism*; D006973:Hypertension / Q000235:genetics*; D007263:Infusions, Parenteral; D008297:Male; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D012727:Sex Characteristics
D006908:Hydroxyprogesterones; C030228:11-hydroxyprogesterone; D000450:Aldosterone; D006913:Hydroxysteroid Dehydrogenases; D042842:11-beta-Hydroxysteroid Dehydrogenases