TY - JOUR
T1 - Protein restriction during pregnancy induces hypertension in adult female rat offspring - Influence of oestradiol
AU - Sathishkumar, K.
AU - Elkins, Rebekah
AU - Yallampalli, Uma
AU - Yallampalli, Chandra
PY - 2012/3/14
Y1 - 2012/3/14
N2 - We previously reported that gestational dietary protein restriction in rats causes sex-related differences in development of blood pressure (BP) in the offspring, which is more pronounced in males than in females. As such effects may depend on sex hormones, we investigated the role of oestradiol in the development of hypertension in female offspring of protein-restricted dams. Female offspring of pregnant rats fed normal (20 %) or protein-restricted (6 %) casein diets throughout pregnancy were kept either intact, ovariectomised or ovariectomised with oestradiol supplementation. BP, Plasma oestradiol and testosterone levels, and vascular oestrogen receptor (ER) were examined. BP was significantly higher and plasma oestradiol levels were significantly lower ( 34 %) in intact protein-restricted female offspring compared to corresponding controls. Further decrease in oestradiol levels by ovariectomy exacerbated hypertension in the protein-restricted females, with an earlier onset and more prominent elevation in BP compared to controls. Oestradiol supplementation in ovariectomised protein-restricted females significantly reversed ovariectomy-induced hypertension but did not normalise BP to control levels. The hypertensive protein-restricted females have reduced vascular ER expression that was unaffected by ovariectomy or oestradiol replacement. In addition, testosterone levels were significantly higher by 2·4-, 3·4- and 2·8-fold in intact, ovariectomised and oestradiol-replaced protein-restricted females compared to corresponding controls. The present data show that: (1) hypertension in protein-restricted adult female offspring is associated with reduced plasma oestradiol levels; (2) oestradiol protects and limits the severity of hypertension in protein-restricted females and contributes to sexual dimorphism; (3) oestradiol replacement fails to completely reverse hypertension, which may be related to limited availability of vascular ER receptors and/or increased circulating testosterone levels.
AB - We previously reported that gestational dietary protein restriction in rats causes sex-related differences in development of blood pressure (BP) in the offspring, which is more pronounced in males than in females. As such effects may depend on sex hormones, we investigated the role of oestradiol in the development of hypertension in female offspring of protein-restricted dams. Female offspring of pregnant rats fed normal (20 %) or protein-restricted (6 %) casein diets throughout pregnancy were kept either intact, ovariectomised or ovariectomised with oestradiol supplementation. BP, Plasma oestradiol and testosterone levels, and vascular oestrogen receptor (ER) were examined. BP was significantly higher and plasma oestradiol levels were significantly lower ( 34 %) in intact protein-restricted female offspring compared to corresponding controls. Further decrease in oestradiol levels by ovariectomy exacerbated hypertension in the protein-restricted females, with an earlier onset and more prominent elevation in BP compared to controls. Oestradiol supplementation in ovariectomised protein-restricted females significantly reversed ovariectomy-induced hypertension but did not normalise BP to control levels. The hypertensive protein-restricted females have reduced vascular ER expression that was unaffected by ovariectomy or oestradiol replacement. In addition, testosterone levels were significantly higher by 2·4-, 3·4- and 2·8-fold in intact, ovariectomised and oestradiol-replaced protein-restricted females compared to corresponding controls. The present data show that: (1) hypertension in protein-restricted adult female offspring is associated with reduced plasma oestradiol levels; (2) oestradiol protects and limits the severity of hypertension in protein-restricted females and contributes to sexual dimorphism; (3) oestradiol replacement fails to completely reverse hypertension, which may be related to limited availability of vascular ER receptors and/or increased circulating testosterone levels.
KW - Blood pressure
KW - Fetal programming
KW - Oestradiol
KW - Sex differences
KW - Sex steroid hormones
KW - Sprague-Dawley rats
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U2 - 10.1017/S0007114511003448
DO - 10.1017/S0007114511003448
M3 - Article
C2 - 21787449
AN - SCOPUS:84856708560
SN - 0007-1145
VL - 107
SP - 665
EP - 673
JO - British Journal of Nutrition
JF - British Journal of Nutrition
IS - 5
ER -