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Does estrogen affect the development of abnormal vascular function in offspring of rats fed a low-protein diet in
Yuka Musha1, Shigeru Itoh, Mark A Hanson
1Department of Obstetrics and Gynecology, School of Medicine Juntendo University 2-1-1 Hongo, Bunkyo-ku Tokyo, Japan 113-8421. yuka-m@med.juntendo.ac.jp
Insights
Maternal protein restriction can lead to hypertension in offspring. Lower estrogen levels exacerbate this condition, suggesting estrogen protects against hypertension development from under-nutrition.
Area of Science:
- Endocrinology
- Cardiovascular Science
- Developmental Biology
Background:
- Gender-specific differences in offspring blood pressure are linked to maternal dietary factors.
- Estrogen levels may influence the onset of hypertension induced by maternal under-nutrition.
Purpose of the Study:
- To investigate the role of estrogen in mediating hypertension development in offspring exposed to maternal protein restriction.
- To determine if reduced estrogen accelerates hypertension onset and alters vascular function.
Main Methods:
- Wistar rats were fed diets with 18% (control) or 9% (restricted) casein during pregnancy.
- Offspring were either ovariectomized or sham-operated to manipulate estrogen levels.
- Vascular reactivity and histological analyses of small arteries were performed at 175 days.
Main Results:
- Offspring from protein-restricted mothers (R) showed higher systolic blood pressure than controls (C) by day 175.
- Ovariectomized offspring from restricted mothers (RX) exhibited earlier onset of elevated blood pressure compared to sham-operated (RO).
- Reduced estrogen impaired acetylcholine and bradykinin-induced vasodilation and increased coronary fibrosis, particularly in ovariectomized rats.
Conclusions:
- Estrogen plays a protective role against hypertension development caused by maternal under-nutrition.
- Estrogen may influence hypertension via bradykinin (BK)-mediated pathways.
- These findings contribute to understanding the developmental origins of hypertension and gender-related differences.
Abstract:
It is established that there are gender-related differences in the effects on offspring blood pressure induced by maternal protein restriction in animal studies. Since such effects may depend on estrogen levels, we hypothesized that lower estrogen would induce an earlier onset of hypertension caused by maternal under-nutrition. Wistar rats were fed a diet containing either 18% (C) or 9% (R) casein throughout pregnancy. Half of the offspring in both C and R groups were ovariectomized on day 50 (CX, RX), and the other half underwent a sham operation (CO, RO). On d 175, offspring were killed for small artery reactivity and histologic investigation. Birth weight and later growth were not significantly different between C and R. RX had higher systolic blood pressure than CX on d125, but no difference was seen between RO and CO. On d 175, systolic blood pressure was higher in R than in C, whether or not ovariectomized. Dilator responses to acetylcholine and bradykinin in small mesenteric arteries were significantly attenuated in RX, although responses to SNP and isoprenaline showed no attenuation in R. The ratio of coronary peri-vascular fibrosis to total vascular area was higher in R, and the fibrosis became prominent in ovariectomized rats. These findings suggest that estrogen plays an important role in limiting the elevation of offspring blood pressure induced by maternal under-nutrition, possibly via BK-mediated mechanisms. The processes may underlie gender and life course patterns of hypertension and also the developmental origins of this disease.
