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Hypertension. 2013 Dec;62(6):1055-61. doi: 10.1161/HYPERTENSIONAHA.113.01983. Epub 2013 Oct 7.

Novel role of the renin-angiotensin system in preeclampsia superimposed on chronic hypertension and the effects of exercise in a mouse model.

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CRCHUM - Technopôle Angus, 2901 Rachel St E, Suite 310, Montreal, Quebec H1W 4A4, Canada.


Gestational hypertensive disorders, such as preeclampsia, affect 6% to 8% of all pregnancies in North America, and they are the leading cause of maternal mortality in industrialized countries, accounting for 16% of deaths. Women with hypertension have an increased risk (15% to 25%) of developing preeclampsia. Our aim was to investigate the mechanisms implicated in preeclampsia superimposed on chronic hypertension and in the protective effects of exercise in a mouse model. Female mice overexpressing human angiotensinogen and human renin were used as a model of preeclampsia superimposed on chronic hypertension. In the trained group, mothers were placed in cages with access to a wheel before mating, and they remained within these throughout gestation. Blood pressure was measured by telemetry. We found that angiotensin II type I receptor was increased, whereas the Mas receptor was decreased in the placenta and the aorta of pregnant sedentary transgenic mice. This would produce a decrease in angiotensin-(1-7) effects in favor of angiotensin II. Supporting the functional contribution of this modulation, we found that the prevention of most pathological features in trained transgenic mice was associated with a normalization of placental angiotensin II type 1 and Mas receptors and an increase in aortic Mas receptor. We also found reduced circulating and placental soluble Fms-like tyrosine kinase-1 in trained transgenic mice compared with sedentary mice. This study demonstrates that modulation of the renin-angiotensin system is a key mechanism in the development of preeclampsia superimposed on chronic hypertension, which can be altered by exercise training to prevent disease features in an animal model.


angiogenic factor; angiotensin-(1–7); exercise; preeclampsia; renin–angiotensin system

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