title: Maintenance of maternal diet-induced hypertension in the rat is dependent on glucocorticoids.
abstract: Recent epidemiological evidence suggests that adult cardiovascular risk is determined by birth weight and factors that influence birth weight, such as maternal nutrition. Data from animal models suggest that an interaction between nutrition and glucocorticoid hormones "programs" increased risk of adult hypertension. Increased fetal exposure to maternal glucocorticoids that is proposed to occur from a reduction in the placental barrier to maternal glucocorticoid, 11beta-hydroxysteroid dehydrogenase, is suggested to program hypertension in the resultant offspring from both glucocorticoid-treated and maternally protein-restricted rats. The extent to which postnatal glucocorticoid stimulation may influence the progression of hypertension in the offspring from protein-restricted rat dams was assessed in 6-week-old male Wistar rats, prenatally exposed to either an 18% casein (control) or 9% casein (low protein) diet. Rats from each dietary group were sham operated, adrenalectomized or adrenalectomized, and treated with 20 mg corticosterone/kg body weight per day. Before surgery, systolic blood pressure was significantly higher in the low protein-exposed rats compared with controls (165+/-3.8 versus 142+/-3.3 mm Hg, P<.0001). Adrenalectomy of the low protein-exposed animals significantly reduced the blood pressure to control levels, while corticosterone replacement restored the hypertensive state. No effect of adrenalectomy on blood pressure was observed in 18% casein controls. In both dietary groups adrenalectomy decreased brain, but not hepatic, glucocorticoid-sensitive enzyme activities and corticosterone treatment elevated activities of all enzymes. The data suggest that maternal diet-induced hypertension is dependent on an intact adrenal gland postnatally and that glucocorticoids are key trophic agents in maintaining the high blood pressure.
authors.affiliation: Institute of Human Nutrition, University of Southampton, Bassett Crescent East Southampton, UK.
authors.forename: D S
authors.initials: DS
authors.lastname: Gardner
authors.forename: A A
authors.initials: AA
authors.lastname: Jackson
authors.forename: S C
authors.initials: SC
authors.lastname: Langley-Evans
mesh_terms: D042842:11-beta-Hydroxysteroid Dehydrogenases; D000315:Adrenalectomy; D000704:Analysis of Variance; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology*; D001921:Brain / Q000201:enzymology; D002364:Caseins; D003345:Corticosterone / Q000494:pharmacology*; D018753:Diet, Protein-Restricted; D004790:Enzyme Induction; D005260:Female; D005974:Glutamate-Ammonia Ligase / Q000096:biosynthesis; D005993:Glycerolphosphate Dehydrogenase / Q000096:biosynthesis; D006913:Hydroxysteroid Dehydrogenases / Q000378:metabolism; D006973:Hypertension / Q000209:etiology / Q000503:physiopathology*; D008099:Liver / Q000201:enzymology; D008291:Malate Dehydrogenase / Q000096:biosynthesis; D008297:Male; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D017208:Rats, Wistar; D014444:Tyrosine Transaminase / Q000096:biosynthesis
chemical_list: D002364:Caseins; D005993:Glycerolphosphate Dehydrogenase; D006913:Hydroxysteroid Dehydrogenases; D042842:11-beta-Hydroxysteroid Dehydrogenases; D008291:Malate Dehydrogenase; D014444:Tyrosine Transaminase; D005974:Glutamate-Ammonia Ligase; D003345:Corticosterone