New Research is Shedding Some Light on the Development of Preeclampsia and Blood Pressure Regulation
Over the last decade much attention has been given to angiotensin-(1-7) (Ang-(1-7)), a component of the renin-angiotensin system (RAS) that has been demonstrated to have a role in blood pressure (BP) regulation during pregnancy.
A new study by researchers at Wake Forest University School of Medicine in collaboration with Dr. Liomar Neves, CorDynamics Senior Scientist, examined the expression profile of Ang-(1-7) and angiotensin II (Ang II) receptors in early and late normal pregnancy and also in a rat model of preeclampsia, the reduced uterine perfusion pressure model (RUPP). The study, funded by the National Institutes of Health, appears in the May issue of Placenta and a figure from the publication is on the front page of the journal.
- Preeclampsia is a very serious condition that affects 7 to 10 percent of all pregnancies in the United States.
- In the US, preeclampsia account for 18% of maternal death, 15% of premature birth and over 100 infant deaths.
- It occurs only during pregnancy and can lead to serious, even fatal, complications for both mother and baby.
- Currently there is no cure except the delivery of the baby and removal of the placenta.
Preeclampsia can be a rapidly progressive condition that impacts multiple body systems, causing high blood pressure, decreased liver function and, in severe cases, affecting the activity of the brain, resulting in seizures.
Swelling, sudden weight gain, headaches and changes in vision are among the symptoms; however, some women with rapidly advancing disease report few symptoms. Despite numerous research studies, the specific causes of preeclampsia remain a mystery.
One possible pathway that has been identified is the RAS, which regulates blood pressure and fluid retention.
The result of many enzymatic pathways that constitute the RAS is the formation of two mainly active peptides, Ang II and Ang-(1-7). Ang II and Ang-(1-7) demonstrate counter-regulatory actions in the control of blood pressure, vasoconstriction, cell proliferation and apoptosis, by binding to their receptors: AT1 and AT2 specific receptors for Ang II and mas/AT1-7 specific receptor for Ang-(1-7). Normal pregnancy is associated with an up-regulation of the systemic RAS, however during preeclampsia the systemic levels of Ang II and Ang-(1-7) are reduced.
Previous studies demonstrated that Ang II is also augmented at late gestation in the rat uterus; however, in a rat model of preeclampsia (the RUPP model), Ang II was reduced in the placenta, while Ang-(1-7) was decreased in the uterus or placenta between RUPP and normal pregnant rats. These data suggest that shifts in the angiotensin peptide profiles within the uteroplacental unit are associated with hypertensive pregnancy. Since the significance of changes in angiotensin peptides is dependent on the distribution and expression of their receptors in the recently published study, the authors looked at the expression and spatial distribution of the angiontensin receptors in the uteroplacental unit.
The expression of mas/AT1-7R, AT2, and AT1R in the uterus at early pregnancy suggest a contribution of Ang-(1-7) and Ang II to maintenance of early pregnancy. During late gestation down-regulation of Ang receptors in the uterus may result from feedback down-regulation due to reduced levels of Ang II. The increased binding of mas/AT1-7R at late gestation in the rat model of preeclampsia may represent a compensatory mechanism to reduce uteroplacental vascular resistance that is increased in preeclampsia.
These findings bring us one step closer to understanding the condition, by getting a picture of what is happening at the maternal and fetal interface, since the placenta is thought to be a key cause of preeclampsia.
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