|RAS in Pregnancy and Preeclampsia and Eclampsia.|
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|PMID: 23346385 Owner: NLM Status: PubMed-not-MEDLINE|
|Preeclampsia is a common disease of pregnancy characterized by the presence of hypertension and commitment of many organs, including the brain, secondary to generalized endothelial dysfunction. Its etiology is not known precisely, but it involved several factors, highlighting the renin angiotensin system (RAS), which would have an important role in the origin of multisystem involvement. This paper reviews the evidence supporting the involvement of RAS in triggering the disease, in addition to the components of this system that would be involved and how it eventually produces brain engagement.|
|M Rodriguez; J Moreno; J Hasbun|
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|Type: Journal Article Date: 2012-12-30|
|Title: International journal of hypertension Volume: 2012 ISSN: 2090-0392 ISO Abbreviation: Int J Hypertens Publication Date: 2012|
|Created Date: 2013-01-24 Completed Date: 2013-01-25 Revised Date: 2013-04-18|
Medline Journal Info:
|Nlm Unique ID: 101538881 Medline TA: Int J Hypertens Country: United States|
|Languages: eng Pagination: 739274 Citation Subset: -|
|Department of Obstetrics and Gynecology, Universidad de Valparaiso, 2341131 Valparaiso, Chile ; Fetal Medicine Unit, Hospital Carlos Van Buren, 2341131 Valparaiso, Chile.|
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Journal ID (nlm-ta): Int J Hypertens
Journal ID (iso-abbrev): Int J Hypertens
Journal ID (publisher-id): IJHT
Publisher: Hindawi Publishing Corporation
Copyright © 2012 M. Rodriguez et al.
Received Day: 22 Month: 11 Year: 2012
Accepted Day: 14 Month: 12 Year: 2012
Print publication date: Year: 2012
Electronic publication date: Day: 30 Month: 12 Year: 2012
Volume: 2012E-location ID: 739274
PubMed Id: 23346385
|RAS in Pregnancy and Preeclampsia and Eclampsia|
1Department of Obstetrics and Gynecology, Universidad de Valparaiso, 2341131 Valparaiso, Chile
2Fetal Medicine Unit, Hospital Carlos Van Buren, 2341131 Valparaiso, Chile
3Fetal Medicine Unit, Hospital Clinico Universidad de Chile, 8380456 Santiago, Chile
|Correspondence: *J. Moreno: email@example.com
[other] Academic Editor: Marc de Gasparo
Preeclampsia is a major complication of pregnancy and corresponds to a major cause of both maternal and fetal morbidity and mortality [1–3]. It is a condition that produces a compromise of many organs, including the brain causing seizures, a condition known as eclampsia [4, 5]. The pathophysiology is not well understood, but it involves different factors, such as genetic, immunological, and inflammatory [6, 7]. In recent years there is a series of studies linking the renin angiotensin system (RAS) with preeclampsia [8–10], in the sense that the alteration of this system would be involved in the pathogenesis of this disease, as this could trigger the different characteristics in this pathology, including brain involvement.
RAS is a system that functions as an important regulator of blood pressure, electrolyte balance, and fluid homeostasis . This system comprises the inactive peptide angiotensinogen, which is converted to angiotensin I and then the active peptide angiotensin II (Ang II) through the action of renin and angiotensin-converting enzyme (ACE) . Ang II exerts its action primarily through the AT1 receptor, located widely in different tissues, including the syncytiotrophoblast .
During pregnancy usually occurs overexpression of many components of the RAS, both in the blood and tissues. There is an increase in plasma renin mainly by extrarenal production . There is also a higher-level production of angiotensinogen liver secondary to increased circulating estrogens. ACE is the only component that has been shown to decrease during normal pregnancy, but equally there is a higher plasma concentration of Ang II [8, 13].
There is an upregulation of RAS components during normal pregnancy, but there is also a decrease in sensitivity to Ang II, whereby these women are resistant to the pressor effect of this molecule, requiring twice Ang II by intravenous infusion compared with nonpregnant women to achieve a similarly vasomotor response .
It is thought that this might be related to the monomer structure of AT1 during uncomplicated pregnancies, unlike the heterodimeric structure observed in terms of sensitivity to Ang II . In addition, estrogens produce a shift in the formation of angiotensin peptides, reducing the formation of Ang II and increasing the production of Ang-(1–7), which has a vasodilator role .
Furthermore, in addition to a systemic RAS, RAS also exists in uteroplacental territory . This unit consists of a placental portion, corresponding to fetal tissue, and a decidual, which is of maternal origin, and in both all components of the RAS are secreted. Therefore, there are 2 RAS systems: placental and decidual. The latter could be related to the pregnancy-associated vascular remodeling of the spiral arteries .
Preeclampsia corresponds to a multisystem disorder characterized by increased peripheral vascular resistance, increased platelet aggregation, and systemic endothelial dysfunction . Corresponds to a multifactorial disease, involving genetic and environmental components, a defective extravillous trophoblast invasion, an impaired immune tolerance between maternal, fetal and placental tissues and maternal inflammatory disorders [19, 20]. Clinically it is characterized by the presence of hypertension and proteinuria from the 2nd half of pregnancy, and the only effective treatment is the termination of pregnancy .
From a physiological point of view, preeclampsia is defined as a disease of two stages . The first is the placental stage that occurs during the first 20 weeks of gestation. In this, the phenomena of remodeling of the vascular walls of the spiral arteries do not develop properly, resulting in abnormal placentation, thus prompting ischemic placenta . The second stage occurs during the second half of pregnancy and is known as the systemic stage. This is the clinical stage of preeclampsia, in which there is an exaggerated maternal systemic inflammatory response and endothelial dysfunction as a central element [24–26]. Between these two stages are some mediators, which are understood as molecules released by the placenta and are capable of transmitting this placental damage and translate into a systemic involvement. Mediators most studied are oxidative stress, microfragments of syncytiotrophoblast (STBM), and antiangiogenic proteins .
There is a considerable amount of evidence supporting the role of angiogenic factors in triggering preeclampsia, and these are the tyrosine-like soluble factor (sFlt-1) and soluble endoglin (s-Eng) [28, 29]. These molecules bind to angiogenic proteins such as VEGF and prevent them from joining their membrane receptors on endothelial cells, leading to endothelial dysfunction . It was observed that these factors are elevated about 6–8 weeks before the start of the clinical picture of preeclampsia, and their plasma concentrations are related to the severity of the disease [31, 32]. In animal models it has been found that inoculation of these can produce hypertension, proteinuria, and hepatic involvement, symptoms characteristic of preeclampsia [33, 34]. It is also observed that hypoxia causes increased secretion of these factors .
In patients with preeclampsia, dysregulation has been observed in the RAS compared to healthy pregnancies. The levels of renin, Ang I, and Ang II are lower than in uncomplicated pregnancies . Despite this decrease in the expression of RAS components, in patients suffering from preeclampsia increased sensitivity to Ang II exists, showing an exaggerated pressor response to Ang II.
In recent years there is a wealth of evidence supporting the AT1 autoantibodies (AT1-AA) in the pathogenesis of preeclampsia. These correspond to IgG autoantibodies that bind to a seven-amino acid sequence present on the second extracellular loop of the AT1 receptor [37, 38]. They are present in the plasma of patients with preeclampsia and are able to increase the beating rate of the cultured cardiomyocytes . Many research papers show that these autoantibodies are elevated in patients with preeclampsia, but not in uncomplicated pregnancies.
In vitro and in vivo studies have determined its role in triggering preeclampsia. These antibodies bind to the AT1 receptors of different cell groups, triggering its pathological action . It has been observed that in human trophoblast cells AT1-AA substances induce the generation of reactive oxygen species (ROS) intracellularly through NDPH oxidase activation . In addition, these same cells stimulate the release of PAI-1, resulting in a decreased trophoblast invasiveness [42, 43], generating a defect of placentation. This increase in PAI-1 is also observed in mesangial cells, which can produce a decrease in extracellular matrix degradation and increased subendothelial fibrin deposition thereby determining renal damage leading to proteinuria and a decreased glomerular filtration rate . It has also been observed that AT1-AA binds to endothelial and vascular cells, causing endothelial damage and vasoconstriction [45, 46].
All these actions could explain endothelial dysfunction, increased peripheral vascular resistance, and impaired coagulation system observed in preeclampsia.
In animal models it has been observed that the inoculation of AT1-AA from patients with preeclampsia is capable of reproducing the characteristics of the disease [47, 48]. Reports in rats showed that surgically induced placental ischemia may cause increased levels of AT1-AA and trigger hypertension and proteinuria [49–51]. It was also observed that these autoantibodies stimulate the release of sFlt-1 and s-eng by the placenta, key proteins in triggering endothelial dysfunction [52, 53].
In the same way pregnant human studies show that placental perfusion abnormality, evaluated with Doppler ultrasound of the uterine arteries, is associated with increased plasma concentrations of AT1-AA before the onset of the disease and that plasmatic levels of these autoantibodies correlate with the severity . The concentration of these autoantibodies is higher in cases of severe preeclampsia, also having a linear correlation with proteinuria and hypertension. This is further confirmed by the fact that in milder cases, as moderate preeclampsia and gestational hypertension, levels of AT1-AA are higher than in normotensive pregnancies, but lower than in severe preeclampsia. Therefore, AT1-AA would be a key element in the pathogenesis of preeclampsia and modulate the secretion of important factors responsible for the pathophysiology .
One of the most serious complications of preeclampsia is eclampsia, which corresponds to the presence of seizures in the context of a patient with hypertension and proteinuria [5, 56]. However, currently the eclampsia is being seen as a manifestation of a much larger entity than pregnancy, known as posterior reversible encephalopathy (PRES), which is produced by other conditions such as hypertensive encephalopathy or use of immunosuppressive drugs. In these cases there is a characteristic increase in blood pressure and/or alteration of endothelial permeability [57–60].
The PRES is characterized by the presence of well-defined signs and symptoms associated with the presence of specific neuroimaging. Among the symptoms are headache, nausea, vomiting, visual disturbances, and seizures [61, 62]. Diagnosis is by observation of symmetrical hyperintense lesions and bilateral parietooccipital level on MRI, suggestive of vasogenic edema .
The exact pathophysiology of PRES is not known with certainty, but is thought to be due to alterations of the vasculature and cerebral perfusion . With the increase in blood pressure, brain responds with its vasculature vasoconstriction, which determines an increase of cerebral perfusion pressure (CPP). As this CPP remains persistently high, it will produce a pressure transmission to the distal small cerebral vessels, causing endothelial damage and muscle dysfunction of cerebral vascular territory [65, 66]. This phenomenon is known as barotrauma, corresponding to forced dilation of arterioles and distal opening of endothelial tight junctions, determining a disruption of the blood-brain barrier (BBB), which leads to increased permeability of this, resulting in a vasogenic edema .
However, not all cases of PRES relate to alterations in arterial pressure. One study shows that 16% of cases of eclampsia occur in normotensive patients, and only 13% of cases were associated with severe hypertension [68, 69]. Therefore, the loss of autoregulation of cerebral perfusion secondary to hypertension does not explain all cases of PRES, so that alteration of endothelial permeability by disruption of the BBB ought to play an important role . A recent study shows that preeclampsia altered BBB permeability independently of blood pressure. In this report it is determined that plasma from patients with preeclampsia significantly increases the permeability of the BBB, compared to plasma from patients with normal pregnancies . These findings support the concept of the pathophysiology of PRES that is determined by hemodynamic factors and factors altering endothelial function.
Various reports have identified the involvement of RAS in the blood-brain barrier disruption in other medical conditions . Therefore, the presence of AT1-AA in patients with preeclampsia could play a key role in triggering PRES. It is shown that these autoantibodies produced an increase in peripheral vascular resistance and hypertension, which leads to a systemic endothelial dysfunction via ROS secretion and antiangiogenic proteins [37, 40], so directly involved in the conditions that can trigger PRES.
Currently, the only effective treatment for preeclampsia is the termination of pregnancy, which in very early pregnancies may not be the best alternative, as this results in increased perinatal morbidity and mortality secondary to prematurity . Therefore, it is important to seek management strategies from the physiological point of view, and in that sense, the management of RAS alteration appears to be a logical choice, given the strong evidence about an excessive AT1 receptor activation during preeclampsia.
Regarding eclampsia, the drug of choice for prevention and management is magnesium sulfate. This drug reduces the risk of seizures in patients with severe preeclampsia . Its mechanism of action is not entirely clear, but it has been shown to be capable of reducing the CPP . However, it should be administered intravenously and usually for 48 hrs, in patient hospitalized and only for short periods of time.
Many studies determined that the addition of losartan (AT1 receptors blocker) or neutralizing antibodies of the AT1-AA (7-amino acid peptide epitope or 7-aa) blocks the effect of AT1-AA, further confirming that the action of these antibodies is through activation of AT1 receptors (z). Animal studies with surgically induced placental ischemia demonstrate that the addition of these compounds significantly reduces arterial pressure , but this effect was not seen with ACE inhibitors . In another report, AT1-AA purified from pregnant women was injected in mice. They triggered hypertension and proteinuria, were significantly reduced or abolished when administered losartan or 7-aa . Adoptive transfer studies in pregnant mice have demonstrated that release of antiangiogenic factors and proinflammatory cytokines resulting from autoantibody-mediated receptor activation is blocked by the addition of 7-aa or AT1 receptor antagonist [10, 37].
The main problem with AT1 receptors blockers is that they increase the risk of fetal malformations, such as oligohydramnios, pulmonary hypoplasia, transient renal failure, preterm delivery, and Potter syndrome [76–78], so its use during pregnancy should be avoided. However, AT1 receptors blockers can be used postpartum, and considering that currently about 30% of eclampsia occur in postpartum [56, 79] and that AT1-AA levels can remain high for a long time , AT1 receptors blockers become an interesting strategy for the management of hypertension during the postpartum period and to decrease the incidence of eclampsia, as well as controlling blood pressure; they block the action of endothelial AT1-AA, which is still present in the postpartum period.
Neutralizing antibodies 7-aa have the advantage of not inhibiting the AT1 receptor; they only block the AT1-AA, without changing completely the action of Ang II. Therefore, it seems a useful strategy for the management of preeclampsia. However, we must await the development of further studies to determine its safety during pregnancy.
During preeclampsia there is an alteration of the RAS. The presence of AT1-AA determines triggering a series of actions in tissues and organs that would result in an increase in peripheral vascular resistance, altered coagulation, renal impairment, and systemic endothelial dysfunction. These alterations can generate the commitment of many organs, including the brain, producing a PRES.
Blocking the action of these autoantibodies using losartan or 7-aa substantially decreases the damage caused by AT1-AA, creating an opportunity for the management and prevention of complications of preeclampsia.
|1.||Sibai B,Dekker G,Kupferminc M. Pre-eclampsiaThe LancetYear: 200536594617857992-s2.0-14644412849|
|2.||Duley L. Maternal mortality associated with hypertensive disorders of pregnancy in Africa, Asia, Latin America and the CaribbeanBritish Journal of Obstetrics and GynaecologyYear: 19929975475532-s2.0-00266333691525093|
|3.||Duley L. The global impact of pre-eclampsia and eclampsiaSeminars in PerinatologyYear: 20093331301372-s2.0-6564912569019464502|
|4.||Norwitz ER,Hsu CD,Repke JT. Acute complications of preeclampsiaClinical Obstetrics and GynecologyYear: 20024523083292-s2.0-003627770312048392|
|5.||Zeeman GG. Neurologic complications of pre-eclampsiaSeminars in PerinatologyYear: 20093331661722-s2.0-6564910452719464507|
|6.||Roberts JM,Cooper DW. Pathogenesis and genetics of pre-eclampsiaThe LancetYear: 2001357924953562-s2.0-0035814640|
|7.||James JL,Whitley GS,Cartwright JE. Pre-eclampsia: fitting together the placental, immune and cardiovascular piecesJournal of PathologyYear: 201022143633782-s2.0-7795549922420593492|
|8.||Shah DM. Role of the renin-angiotensin system in the pathogenesis of preeclampsiaAmerican Journal of PhysiologyYear: 20052884F614F6252-s2.0-1504434824615753325|
|9.||Irani RA,Xia Y. The functional role of the renin-angiotensin system in pregnancy and preeclampsiaPlacentaYear: 20082997637712-s2.0-5004912884118687466|
|10.||Irani RA,Xia Y. Renin angiotensin signaling in normal pregnancy and preeclampsiaSeminars in NephrologyYear: 201131147582-s2.0-7875168473421266264|
|11.||Shah DM. The role of RAS in the pathogenesis of preeclampsiaCurrent Hypertension ReportsYear: 20058214415216672148|
|12.||Welches WR,Brosnihan KB,Ferrario CM. A comparison of the properties and enzymatic activities of three angiotensin processing enzymes: angiotensin converting enzyme, prolyl endopeptidase and neutral endopeptidase 24.11Life SciencesYear: 19935218146114802-s2.0-00274068618387132|
|13.||Anton L,Brosnihan KB. Systemic and uteroplacental renin-angiotensin system in normal and pre-eclamptic pregnanciesTherapeutic Advances in Cardiovascular DiseaseYear: 2008253493622-s2.0-6564914228519124433|
|14.||Abdul-Karim R,Assali NS. Pressor response to angiotensin in pregnant and non-pregnant womenAmerican Journal of Obstetrics and GynecologyYear: 19618224625113680954|
|15.||AbdAlla S,Lother H,El Massiery A,Quitterer U. Increased AT1 receptor heterodimers in preeclampsia mediate enhanced angiotensin II responsivenessNature MedicineYear: 200179100310092-s2.0-0034785580|
|16.||Brosnihan KB,Neves LAA,Anton L,Joyner J,Valdes G,Merrill DC. Enhanced expression of Ang-(1–7) during pregnancyBrazilian Journal of Medical and Biological ResearchYear: 2004378125512622-s2.0-444422269015273828|
|17.||Morgan T,Craven C,Lalouel JM,Ward K. Angiotensinogen Thr235 variant is associated with abnormal physiologic change of the uterine spiral arteries in first-trimester deciduaAmerican Journal of Obstetrics and GynecologyYear: 19991801 I951022-s2.0-00330244759914585|
|18.||Poston L. Endothelial dysfunction in pre-eclampsiaPharmacological ReportsYear: 20065869742-s2.0-3534883709217332674|
|19.||Redman CWG,Sargent IL. Placental stress and pre-eclampsia: a revised viewPlacentaYear: 200930S38S422-s2.0-6024910303219138798|
|20.||Kaufmann P,Black S,Huppertz B. Endovascular trophoblast invasion: implications for the pathogenesis of intrauterine growth retardation and preeclampsiaBiology of ReproductionYear: 2003691172-s2.0-003811315512620937|
|21.||ACOG Committee on Obstetric PracticeACOG practice bulletin. Diagnosis and management of preeclampsia and eclampsia. Number 33, January 2002. American college of obstetricians and gynecologistsInternational Journal of Gynecology and ObstetricsYear: 2002771677512094777|
|22.||Redman CW,Sargent IL. Latest advances in understanding preeclampsiaScienceYear: 20053085728159215942-s2.0-2044440913515947178|
|23.||Chaddha V,Viero S,Huppertz B,Kingdom J. Developmental biology of the placenta and the origins of placental insufficiencySeminars in Fetal and Neonatal MedicineYear: 2004953573692-s2.0-1274425478015691771|
|24.||Redman CWG,Sargent IL. Pre-eclampsia, the placenta and the maternal systemic inflammatory response—a reviewPlacentaYear: 200324S21S272-s2.0-014183813312842410|
|25.||Bernardi F,Guolo F,Bortolin T,Petronilho F,Dal-Pizzol F. Oxidative stress and inflammatory markers in normal pregnancy and preeclampsiaJournal of Obstetrics and Gynaecology ResearchYear: 20083469489512-s2.0-5564909794319012691|
|26.||Granger JP,Alexander BT,Llinas MT,Bennett WA,Khalil RA. Pathophysiology of preeclampsia: linking placental ischemia/hypoxia with microvascular dysfunctionMicrocirculationYear: 2002931471602-s2.0-003665420712080413|
|27.||Levine RJ,Karumanchi SA. Circulating angiogenic factors in preeclampsiaClinical Obstetrics and GynecologyYear: 20054823723862-s2.0-1804437064315805796|
|28.||Maynard S,Epstein FH,Karumanchi SA. Preeclampsia and angiogenic imbalanceAnnual Review of MedicineYear: 20085961782-s2.0-39649101109|
|29.||Wang A,Rana S,Karumanchi SA. Preeclampsia: the role of angiogenic factors in its pathogenesisPhysiologyYear: 20092431471582-s2.0-6764922764719509125|
|30.||Kendall RL,Thomas KA. Inhibition of vascular endothelial cell growth factor activity by an endogenously encoded soluble receptorProceedings of the National Academy of Sciences of the United States of AmericaYear: 1993902210705107092-s2.0-00274213338248162|
|31.||Levine RJ,Maynard SE,Qian C,et al. Circulating angiogenic factors and the risk of preeclampsiaThe New England Journal of MedicineYear: 200435076726832-s2.0-1074422719914764923|
|32.||Levine RJ,Lam C,Qian C,et al. Soluble endoglin and other circulating antiangiogenic factors in preeclampsiaThe New England Journal of MedicineYear: 20063551099210052-s2.0-3374842166016957146|
|33.||Maynard SE,Min JY,Merchan J,et al. Excess placental soluble fms-like tyrosine kinase 1 (sFlt1) may contribute to endothelial dysfunction hypertension, and proteinuria in preeclampsiaJournal of Clinical InvestigationYear: 200311156496582-s2.0-003737300612618519|
|34.||Venkatesha S,Toporsian M,Lam C,et al. Soluble endoglin contributes to the pathogenesis of preeclampsiaNature MedicineYear: 20061266426492-s2.0-33744985816|
|35.||Makris A,Thornton C,Thompson J,et al. Uteroplacental ischemia results in proteinuric hypertension and elevated sFLT-1Kidney InternationalYear: 200771109779842-s2.0-3424834133217377512|
|36.||Herse F,Staff AC,Hering L,Müller DN,Luft FC,Dechend R. AT1-receptor autoantibodies and uteroplacental RAS in pregnancy and pre-eclampsiaJournal of Molecular MedicineYear: 20088666977032-s2.0-4344913406418398593|
|37.||Xia Y,Cissy CZ,Ramin SM,Kellems RE. Angiotensin receptors, autoimmunity, and preeclampsiaJournal of ImmunologyYear: 20071796339133952-s2.0-35748966703|
|38.||Xia Y,Kellems R. Receptor-activating autoantibodiesand disease: preeclampsia and bevondExpert Review of Clinical ImmunologyYear: 20117565967421895478|
|39.||Wallukat G,Homuth V,Fischer T,et al. Patients with preeclampsia develop agonistic autoantibodies against the angiotensin AT1 receptorJournal of Clinical InvestigationYear: 199910379459522-s2.0-003292492210194466|
|40.||LaMarca B,Wallace K,Granger J. Role of angiotensin II type I receptor agonistic autoantibodies (AT1-AA) in preeclampsiaCurrent Opinion in PharmacologyYear: 201111217517921317038|
|41.||Dechend R,Viedt C,Müller DN,et al. AT1 receptor agonistic antibodies from preeclamptic patients stimulate NADPH oxidaseCirculationYear: 200310712163216392-s2.0-003738401612668498|
|42.||Xia Y,Wen HY,Kellems RE. Angiotensin II inhibits human trophoblast invasion through AT1 receptor activationThe Journal of Biological ChemistryYear: 20022772724601246082-s2.0-003702532011983698|
|43.||Xia Y,Wen H,Bobst S,Day MC,Kellems RE. Maternal autoantibodies from preeclamptic patients activate angiotensin receptors on human trophoblast cellsJournal of the Society for Gynecologic InvestigationYear: 200310282932-s2.0-003731709012593997|
|44.||Bobst SM,Day MC,Gilstrap LC,Xia Y,Kellems RE. Maternal autoantibodies from preeclamptic patients activate angiotensin receptors on human mesangial cells and induce interleukin-6 and plasminogen activator inhibitor-1 secretionAmerican Journal of HypertensionYear: 20051833303362-s2.0-1574438294315797649|
|45.||Dechend R,Homuth V,Wallukat G,et al. AT1 receptor agonistic antibodies from preeclamptic patients cause vascular cells to express tissue factorCirculationYear: 200010120238223872-s2.0-003470499910821814|
|46.||Yang X,Wang F,Chang H,et al. Autoantibody against AT1 receptor from preeclamptic patients induces vasoconstriction through angiotensin receptor activationJournal of HypertensionYear: 2008268162916352-s2.0-5154908350418622242|
|47.||Zhou CC,Zhang Y,Irani RA,et al. Angiotensin receptor agonistic autoantibodies induce pre-eclampsia in pregnant miceNature MedicineYear: 200814855862|
|48.||LaMarca B,Parrish M,Ray LF,et al. Hypertension in response to autoantibodies to the angiotensin II type i receptor (AT1-AA) in pregnant rats: role of endothelin-1HypertensionYear: 20095449059092-s2.0-7034968042119704104|
|49.||LaMarca B,Wallukat G,Llinas M,Herse F,Dechend R,Granger JP. Autoantibodies to the angiotensin type I receptor in response to placental ischemia and tumor necrosis factor α in pregnant ratsHypertensionYear: 2008526116811722-s2.0-5744910234518852381|
|50.||Granger JP,LaMarca BB,Cockrell K,et al. Reduced uterine perfusion pressure (RUPP) model for studying cardiovascular-renal dysfunction in response to placental ischemiaMethods in Molecular MedicineYear: 20061223833922-s2.0-3364591703516511995|
|51.||LaMarca BB,Bennett WA,Alexander B,et al. Hypertension produced by reductions in uterine perfusion in the pregnant rat: role of tumor necrosis factor-αHypertensionYear: 2005464102210252-s2.0-3364464221416144982|
|52.||Zhou CC,Ahmad S,Mi T,et al. Autoantibody from women with preeclampsia induces soluble Fms-like tyrosine kinase-1 production via angiotensin type 1 receptor and calcineurin/nuclear factor of activated T-cells signalingHypertensionYear: 2008514101010192-s2.0-4084910512818259044|
|53.||Zhou CC,Irani RA,Zhang Y,et al. Angiotensin receptor agonistic autoantibody-mediated tumor necrosis factor-α induction contributes to increased soluble endoglin production in preeclampsiaCirculationYear: 201012134364442-s2.0-7664911807020065159|
|54.||Walther T,Wallukat G,Jank A,et al. Angiotensin II type 1 receptor agonistic antibodies reflect fundamental alterations in the uteroplacental vasculatureHypertensionYear: 2005466127512792-s2.0-3194445145716260641|
|55.||Siddiqui AH,Irani RA,Blackwell SC,Ramin SM,Kellems RE,Xia Y. Angiotensin receptor agonistic autoantibody is highly prevalent in preeclampsia: correlation with disease severityHypertensionYear: 20105523863932-s2.0-7494910657419996068|
|56.||Sibai BM. Diagnosis, prevention, and management of eclampsiaObstetrics and GynecologyYear: 200510524024102-s2.0-1354427788515684172|
|57.||Hinchey J,Chaves C,Appignani B,et al. A reversible posterior leukoencephalopathy syndromeThe New England Journal of MedicineYear: 199633484945002-s2.0-133442846358559202|
|58.||Tollemar J,Ringden O,Ericzon BG,et al. Cyclosporine-associated central nervous system toxicityThe New England Journal of MedicineYear: 1988318127887892-s2.0-00238497273347234|
|59.||Sloane JP,Lwin KY,Gore ME,et al. Disturbannce of blood-brain barrier after bone-marrow transplantationThe LancetYear: 1985284492802812-s2.0-0021892717|
|60.||Verbeke M,van de Voorde J,de Ridder L,Lameire N. Functional analysis of vascular dysfunction in cyclosporin treated ratsCardiovascular ResearchYear: 1994288115211562-s2.0-00280304667954616|
|61.||Lee VH,Wijdicks EFM,Manno EM,Rabinstein AA. Clinical spectrum of reversible posterior leukoencephalopathy syndromeArchives of NeurologyYear: 20086522052102-s2.0-3904913981518268188|
|62.||Bartynski WS. Posterior reversible encephalopathy syndrome, part 1: fundamental imaging and clinical featuresAmerican Journal of NeuroradiologyYear: 2008296103610422-s2.0-4674915587618356474|
|63.||Bartynski WS,Boardman JF. Distinct imaging patterns and lesion distribution in posterior reversible encephalopathy syndromeAmerican Journal of NeuroradiologyYear: 2007287132013272-s2.0-3454816281417698535|
|64.||Oehm E,Reinhard M,Keck C,Els T,Spreer J,Hetzel A. Impaired dynamic cerebral autoregulation in eclampsiaUltrasound in Obstetrics and GynecologyYear: 20032243953982-s2.0-014210629014528476|
|65.||Oehm E,Hetzel A,Els T,et al. Cerebral hemodynamics and autoregulation in reversible posterior leukoencephalopathy syndrome caused by pre-/eclampsiaCerebrovascular DiseasesYear: 2006222-32042082-s2.0-3374632928216766873|
|66.||Belfort MA,Varner MW,Dizon-Townson DS,Grunewald C,Nisell H. Cerebral perfusion pressure, and not cerebral blood flow, may be the critical determinant of intracranial injury in preeclampsia: a new hypothesisAmerican Journal of Obstetrics and GynecologyYear: 200218736266342-s2.0-003673899712237639|
|67.||Cipolla MJ. Cerebrovascular function in pregnancy and eclampsiaHypertensionYear: 200750114242-s2.0-3425085413017548723|
|68.||Mattar F,Sabai BM. Eclampsia. VIII. Risk factors for maternal mortalityAmerican Journal of Obstetrics and GynecologyYear: 2000182230731210694329|
|69.||Sibai BM. Eclampsia. VI. Maternal-perinatal outcome in 254 ocnsecutive casesAmerican Journal of Obstetrics and GynecologyYear: 19901633104910552-s2.0-00250017472403130|
|70.||Amburgey O,Chapman AC,May V,Bernstein IM,Cipolla MJ. Plasma from preeclamptic women increases blood-brain barrier permeability: role of vascular endothelial growth factor signalingHypertensionYear: 2010565100310082-s2.0-7814926812820855653|
|71.||Pelisch N,Hosomi N,Ueno M,et al. Blockade of AT1 receptors protects the blood-brain barrier and improves cognition in dahl salt-sensitive hypertensive ratsAmerican Journal of HypertensionYear: 20112433623682-s2.0-7995167753221164491|
|72.||Sibai BM. Diagnosis and management of gestational hypertension and preeclampsiaObstetrics and GynecologyYear: 200310211811922-s2.0-003770788912850627|
|73.||Altman D,Carroli G,Duley L,et al. Do women with pre-eclampsia, and their babies, benefit from magnesium sulphate? The Magpie trial: a randomised placebo-controlled trialThe LancetYear: 20023599321187718902-s2.0-0036606736|
|74.||Belfort M,Allred J,Dildy G. Magnesium sulfate decreases cerebral perfusion pressure in preeclampsiaHypertension in PregnancyYear: 20082743153272-s2.0-5604909528619003633|
|75.||Alexander BT,Cockrell K,Cline FD,Llinas MT,Sedeek M,Granger JP. Effect of angiotensin II synthesis blockade on the hypertensive response to chronic reductions in uterine perfusion pressure in pregnant ratsHypertensionYear: 20013837427452-s2.0-003546311411566968|
|76.||Roger N,Popovic I,Madelenat P,Mahieu-Caputo D. Fetal toxicity of angiotensin-II-receptor inhibitors. Case reportGynecologie Obstetrique FertiliteYear: 20073565565602-s2.0-34250310864|
|77.||Bos-Thompson MA,Hillarire-Buys D,Muller F,et al. Fetal toxic effects of angiotensin II receptor antagonists: case report and follow-up after birthThe Annals of PharmacotherapyYear: 200539115716115590878|
|78.||Kato K,Okuda M,Ishikawa H,Takahashi T,Hirahara F. Oligohydramnios and pulmonary hypoplasia: a case in which involvement of an angiotensin II receptor antagonist was suspectedJournal of Obstetrics and Gynaecology ResearchYear: 20083422422462-s2.0-4214916352018412789|
|79.||Hubel CA,Wallukat G,Wolf M,et al. Agonistic angiotensin II type 1 receptor autoantibodies in postpartum women with a history of preeclampsiaHypertensionYear: 20074936126172-s2.0-3384706549917210828|
|80.||Chames MC,Livingston JC,Invster TS,et al. Late postpartum eclampsia: a preventable disease?American Journal of Obstetrics and GynecologyYear: 200218661174117712066093|
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