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ABSTRACT: A low-protein diet (LPD) during pregnancy induces vascular dysfunction and hypertension in the offspring, prevented by administration of an angiotensin II type 1 (AT(1)) receptor antagonist in early life to the offspring. Whether such protection extends to subsequent pregnancy is unknown; we therefore hypothesized that administration of a specific AT(1) receptor antagonist (losartan) in early life to offspring of LPD dams would improve vascular dysfunction in their uterine arteries when they, in turn, were pregnant.
Pregnant rats were randomly divided into two dietary groups fed a control (C) or protein-restricted (R) diet throughout pregnancy. Between two and 10 weeks postnatally, female offspring (F(1)) were randomly assigned to drink either pure tap water (CO, RO) or water with losartan (CL, RL). Offspring were mated and killed on gestational day 19 or 20 in order to investigate uterine artery function.
In pregnant offspring, vasoconstriction of the uterine arteries to phenylephrine (PE) and the thromboxane A2 mimetic U46619 was greater in RO than CO (F(1)). Responses to both antagonists were suppressed in RL (F(1)). Relaxation to sodium nitroprusside was increased in RO versus CO and suppressed in RL versus RO (F(1)).
Administration of an AT(1) receptor antagonist to offspring during the suckling and juvenile period improves the uterine vascular dysfunction in pregnancy induced by prior maternal LPD during their development. Such treatment may contribute to decreasing the transmitted risks of maternal malnutrition from offspring to the subsequent generation.
Journal of Obstetrics and Gynaecology Research 03/2012; 38(3):483-9. · 0.84 Impact Factor
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ABSTRACT: Our previous study showed that a maternal low-protein diet induced hypertension and vascular dysfunction in rat offspring after day 175. In the present study, we hypothesized that these female offspring would develop hypertension in their own pregnancies even at ages less than 175 days because potential vascular dysfunction is exacerbated by the circulatory demands of pregnancy.
Wistar rats were fed an isocaloric diet containing either 18% (control group) or 9% (low-protein group) casein throughout pregnancy. The female offspring were fed standard chow and mated between days 70 and 125. At the end of pregnancy, blood pressure was measured, and the uterine arteries were dissected and investigated with a wire myograph.
Placental weights were significantly lower in offspring of the low-protein group versus control. There were no significant differences in blood pressure. Renal expression of AT1 receptor mRNA was greater, and of AT2 receptor was less, in the low-protein group versus control. Vasoconstriction of uterine arteries to phenylephrine and U46619 was increased in the low-protein group, and vasodilatation to sodium nitroprusside was also increased.
Low-protein diet induces vascular effects on female offspring in their pregnancy, in terms of increased uterine artery vasoconstriction. This may be compensated for by increased sensitivity to nitric oxide (NO), maintaining blood pressure normal in the face of the demands of pregnancy. Such renal and vascular effects, combined with placental size, may transmit risk of vascular dysfunction to subsequent generations.
Journal of Obstetrics and Gynaecology Research 04/2011; 37(4):343-51. · 0.84 Impact Factor
Early Human Development 09/2007; 83. · 1.93 Impact Factor