The early life programming of adult hypertension by glucocorticoids
The early life programming of adult hypertension by glucocorticoids
The thesis presented examines the role of glucocorticoids in a model of hypertension programmed by maternal nutrition.
A low protein, isoenergetic diet (MLP) in the rat reduced maternal weight gain in late gestation and impaired the activity of placental 11β-hydroxysteroid dehydrogenase Type 2 at day 20 gestation, which changes in maternal hormonal status could not explain. MLP fetuses may therefore be exposed to a greater level of maternal glucocorticoid in late gestation. MLP pups at term were of low to normal birthweight yet exhibited degrees of disproportionate intrauterine growth that appeared to favour maintenance of substrate supply to the brain. Brain growth was maintained in proportion to growth of the body whereas growth of the liver, lungs and trunk was not.
MLP pups from term, into adulthood, demonstrated increased activities of glucocorticoid-inducible enzymes despite normal plasma corticosterone concentrations indicating a degree of hypersensitivity to glucocorticoid action. MLP pups were hypertensive relative to control rats from weaning age. Maternal adrenalectomy successfully ablated the hypertensive state of MLP-male rats which corticosterone, but not aldosterone, replacement to pregnant adrenalectomized rats restored. Hypertension in MLP-males is therefore likely to be glucocorticoid-dependent. Hypertension in MLP-female rats was either delayed or unaffected by maternal adrenalectomy, however, corticosterone replacement to MLP dams elevated the systolic blood pressure of MLP-female offspring.
The data suggest that maternal undernutrition through maternal glucocortoid influence, programmes hypertension in the resultant offspring in the rat. Increased sensitivity to glucocorticoid and angiotensin II action may partially maintain the hypertensive state. Undernutrition-induced fetal over-exposure to predominantly maternal glucocorticoids may contribute to mechanisms underpinning the incidence of adult hypertension associated with low birthweight.
University of Southampton
Gardner, David Stuart
a9545a8a-4046-4355-818d-024e711043e6
1998
Gardner, David Stuart
a9545a8a-4046-4355-818d-024e711043e6
Gardner, David Stuart
(1998)
The early life programming of adult hypertension by glucocorticoids.
University of Southampton, Doctoral Thesis.
Record type:
Thesis
(Doctoral)
Abstract
The thesis presented examines the role of glucocorticoids in a model of hypertension programmed by maternal nutrition.
A low protein, isoenergetic diet (MLP) in the rat reduced maternal weight gain in late gestation and impaired the activity of placental 11β-hydroxysteroid dehydrogenase Type 2 at day 20 gestation, which changes in maternal hormonal status could not explain. MLP fetuses may therefore be exposed to a greater level of maternal glucocorticoid in late gestation. MLP pups at term were of low to normal birthweight yet exhibited degrees of disproportionate intrauterine growth that appeared to favour maintenance of substrate supply to the brain. Brain growth was maintained in proportion to growth of the body whereas growth of the liver, lungs and trunk was not.
MLP pups from term, into adulthood, demonstrated increased activities of glucocorticoid-inducible enzymes despite normal plasma corticosterone concentrations indicating a degree of hypersensitivity to glucocorticoid action. MLP pups were hypertensive relative to control rats from weaning age. Maternal adrenalectomy successfully ablated the hypertensive state of MLP-male rats which corticosterone, but not aldosterone, replacement to pregnant adrenalectomized rats restored. Hypertension in MLP-males is therefore likely to be glucocorticoid-dependent. Hypertension in MLP-female rats was either delayed or unaffected by maternal adrenalectomy, however, corticosterone replacement to MLP dams elevated the systolic blood pressure of MLP-female offspring.
The data suggest that maternal undernutrition through maternal glucocortoid influence, programmes hypertension in the resultant offspring in the rat. Increased sensitivity to glucocorticoid and angiotensin II action may partially maintain the hypertensive state. Undernutrition-induced fetal over-exposure to predominantly maternal glucocorticoids may contribute to mechanisms underpinning the incidence of adult hypertension associated with low birthweight.
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Published date: 1998
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Local EPrints ID: 463475
URI: http://eprints.soton.ac.uk/id/eprint/463475
PURE UUID: 5db01ede-bae2-4cbd-b8a6-7b1e50376b95
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Date deposited: 04 Jul 2022 20:52
Last modified: 16 Mar 2024 19:04
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Author:
David Stuart Gardner
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