Inhibition of 11 beta-hydroxysteroid dehydrogenase in pregnant rats and the programming of blood pressure in the offspring

被引:258
作者
Lindsay, RS
Lindsay, RM
Edwards, CRW
Seckl, JR
机构
[1] Department of Medicine, University of Edinburgh, Western General Hospital, Edinburgh
[2] Department of Medicine, University of Edinburgh, Western General Hospital
基金
英国惠康基金;
关键词
blood pressure; corticosterone; birth weight; glucocorticoid; carbenoxolone;
D O I
10.1161/01.HYP.27.6.1200
中图分类号
R6 [外科学];
学科分类号
1002 ; 100210 ;
摘要
Recent epidemiological studies have linked low birth weight with the later occurrence of cardiovascular and metabolic disorders, particularly hypertension. We have proposed that fetal exposure to excess maternal glucocorticoids may underpin this association. Normally, the fetus is protected from maternal glucocorticoids by placental 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD). We have previously shown that treatment of pregnant rats with dexamethasone, a synthetic glucocorticoid that is poorly metabolized by the enzyme, reduces birth weight and produces elevated blood pressure in the adult offspring. Moreover, low activity of placental 11 beta-HSD correlates with low birth weight in rats. Here, we show that maternal administration of carbenoxolone, a potent inhibitor of 11 beta-HSD, throughout pregnancy leads to reduced birth weight (mean 20% decrease) and elevated blood pressures (increase in mean arterial pressure, 9 mm Hg in males, 7 mm Hg in females) in the adult offspring of carbenoxolone-treated rats. This effect requires the of presence of maternal adrenal products, as carbenoxolone given to adrenalectomized pregnant rats had no effect on birth weight or blood pressure. These data support the hypothesis that excess exposure of the fetoplacental unit to maternal glucocorticoids reduces birth weight and programs subsequent hypertension and indicate a key role for placental 11 beta-HSD in controlling such exposure.
引用
收藏
页码:1200 / 1204
页数:5
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