The renin–angiotensin–aldosterone system in pre-eclampsia: the delicate balance between good and bad

Clinical Science - Tập 126 Số 8 - Trang 537-544 - 2014
Koen Verdonk1, W. Edward Visser2, Anton H. van den Meiracker1, A.H. Jan Danser1
1Department of Internal Medicine, Division of Vascular Medicine and Pharmacology, Erasmus MC, Rotterdam, The Netherlands
2Department of Obstetrics and Gynecology, Division Obstetrics & Prenatal Medicine, Erasmus MC, Rotterdam, The Netherlands

Tóm tắt

Pregnancy demands major changes of the cardiovascular system, and this involves, among others, activation of the RAAS (renin–angiotensin–aldosterone system), allowing an aldosterone-dependent increase in volume. Remarkably, a relative resistance to the pressor response of AngII (angiotensin II) develops simultaneously to prevent the increase in blood pressure that would normally accompany RAAS activation. The increase in volume, the degree of RAAS activation and the diminished pressor response to AngII are less pronounced in pre-eclampsia. However, animal models displaying excessive RAAS activation also result in a pre-eclampsia-like syndrome, and the aldosterone/renin ratio is elevated in pre-eclampsia compared with a normal pregnancy. New insights into the pathogenesis of pre-eclampsia have revealed a major role for VEGF (vascular endothelial growth factor), VEGF-inactivating sFlt-1 (soluble fms-like tyrosine kinase-1) and AT1 (angiotensin II type 1) receptor autoantibodies. The last mentioned activate AT1 receptors, thereby potentially suppressing circulating renin and aldosterone. VEGF, both directly and indirectly (by increasing capillary density), affects adrenal aldosterone synthesis. The present review summarizes all of the recent findings regarding RAAS regulation in pre-eclampsia compared with normal pregnancy, concluding that factors such as sFlt-1 and AT1 receptor autoantibodies disturb the delicate balance that normally results in a volume increase and a diminished vasoconstrictor response to AngII in pregnant women. It is possible that there are non-parallel changes in the circulating and renal RAAS in pre-eclampsia, which are potentially reflected by the urinary levels of renin.

Từ khóa


Tài liệu tham khảo

Steegers, 2010, Pre-eclampsia, Lancet, 376, 631, 10.1016/S0140-6736(10)60279-6

Verlohren, 2012, Angiogenic growth factors in the diagnosis and prediction of pre-eclampsia, Clin. Sci., 122, 43, 10.1042/CS20110097

Rana, 2012, Angiogenic factors and the risk of adverse outcomes in women with suspected preeclampsia, Circulation, 125, 911, 10.1161/CIRCULATIONAHA.111.054361

Verdonk, 2012, Differential diagnosis of preeclampsia remember the soluble fms-like tyrosine kinase 1/placental growth factor ratio, Hypertension, 60, 884, 10.1161/HYPERTENSIONAHA.112.201459

Gilbert, 2007, Hypertension produced by reduced uterine perfusion in pregnant rats is associated with increased soluble fms-like tyrosine kinase-1 expression, Hypertension, 50, 1142, 10.1161/HYPERTENSIONAHA.107.096594

Maynard, 2003, Excess placental soluble fms-like tyrosine kinase 1 (sflt1) may contribute to endothelial dysfunction, hypertension, and proteinuria in preeclampsia, J. Clin. Invest., 111, 649, 10.1172/JCI17189

Herse, 2007, Dysregulation of the circulating and tissue-based renin-angiotensin system in preeclampsia, Hypertension, 49, 604, 10.1161/01.HYP.0000257797.49289.71

Williams, 1997, Nitric oxide-mediated vasodilation in human pregnancy, Am. J. Physiol., 272, H748

Brown, 1994, Volume homeostasis in normal pregnancy and pre-eclampsia: physiology and clinical implications, Baillieres Clin. Obstet. Gynaecol., 8, 287, 10.1016/S0950-3552(05)80322-0

Moran, 2004, The renal response to preeclampsia, Semin. Nephrol., 24, 588, 10.1016/j.semnephrol.2004.07.008

Salas, 2006, Time course of maternal plasma volume and hormonal changes in women with preeclampsia or fetal growth restriction, Hypertension, 47, 203, 10.1161/01.HYP.0000200042.64517.19

Visser, 1991, Central hemodynamic observations in untreated preeclamptic patients, Hypertension, 17, 1072, 10.1161/01.HYP.17.6.1072

Tewksbury, 1996, Quantitation of five forms of high molecular weight angiotensinogen from human placenta, Am. J. Hypertens., 9, 1029, 10.1016/0895-7061(96)00175-6

Tewksbury, 1982, High molecular-weight angiotensinogen levels in hypertensive pregnant-women, Hypertension, 4, 729, 10.1161/01.HYP.4.5.729

Kloverpris, 2013, Formation of high-molecular-weight angiotensinogen during pregnancy is a result of competing redox reactions with the proform of eosinophil major basic protein, Biochem. J., 449, 209, 10.1042/BJ20120801

Brown, 1988, Sodium renin aldosterone relations in normal and hypertensive pregnancy, Br. J. Obstet. Gynaecol., 95, 1237, 10.1111/j.1471-0528.1988.tb06812.x

Zhou, 2010, A redox switch in angiotensinogen modulates angiotensin release, Nature, 468, 108, 10.1038/nature09505

Batenburg, 2007, Prorenin is the endogenous agonist of the (pro)renin receptor. Binding kinetics of renin and prorenin in rat vascular smooth muscle cells overexpressing the human (pro) renin receptor, J. Hypertens., 25, 2441, 10.1097/HJH.0b013e3282f05bae

Shahvaisizadeh, 2012, Synergistic effects of angiotensinogen -217 G→A and T704C (M235T) variants on the risk of severe preeclampsia, JRAAS

Danser, 1998, Determinants of interindividual variation of renin and prorenin concentrations: evidence for a sexual dimorphism of (pro)renin levels in humans, J. Hypertens., 16, 853, 10.1097/00004872-199816060-00017

Morgan, 2006, Hypervolemia of pregnancy is not maintained in mice chronically overexpressing angiotensinogen, Am. J. Obstet. Gynecol., 195, 1700, 10.1016/j.ajog.2006.04.005

Takimoto, 1996, Hypertension induced in pregnant mice by placental renin and maternal angiotensinogen, Science, 274, 995, 10.1126/science.274.5289.995

Verlohren, 2010, Inhibition of trophoblast-induced spiral artery remodeling reduces placental perfusion in rat pregnancy, Hypertension, 56, 304, 10.1161/HYPERTENSIONAHA.110.153163

Bohlender, 2000, Rats transgenic for human renin and human angiotensinogen as a model for gestational hypertension, J. Am. Soc. Nephrol., 11, 2056, 10.1681/ASN.V11112056

Derkx, 1987, Source of plasma prorenin in early and late pregnancy: observations in a patient with primary ovarian failure, J. Clin. Endocrinol. Metab., 65, 349, 10.1210/jcem-65-2-349

Spaan, 2012, Renin–angiotensin system in pre-eclampsia: everything old is new again, Obstet. Med., 5, 147, 10.1258/om.2012.120007

Krop, 2008, Circulating versus tissue renin–angiotensin system: on the origin of (pro)renin, Curr. Hypertens. Reports, 10, 112, 10.1007/s11906-008-0022-1

Nguyen, 2002, Pivotal role of the renin/prorenin receptor in angiotensin II production and cellular responses to renin, J. Clin. Invest., 109, 1417, 10.1172/JCI0214276

Batenburg, 2011, Renin- and prorenin-induced effects in rat vascular smooth muscle cells overexpressing the human (pro)renin receptor: does (pro)renin–(pro)renin receptor interaction actually occur?, Hypertension, 58, 1111, 10.1161/HYPERTENSIONAHA.111.180737

Ringholm, 2011, A high concentration of prorenin in early pregnancy is associated with development of pre-eclampsia in women with type 1 diabetes, Diabetologia, 54, 1615, 10.1007/s00125-011-2087-7

Nochy, 1984, Diminished number of renin-containing cells in kidney biopsy samples from hypertensive women immediately postpartum–an immunomorphologic study, Kidney Int., 26, 85, 10.1038/ki.1984.138

Miyamoto, 1988, Circadian rhythm of plasma atrial natriuretic peptide, aldosterone, and blood pressure during the third trimester in normal and preeclamptic pregnancies, Am. J. Obstet. Gynecol., 158, 393, 10.1016/0002-9378(88)90162-7

Kappers, 2010, Hypertension induced by the tyrosine kinase inhibitor sunitinib is associated with increased circulating endothelin-1 levels, Hypertension, 56, 675, 10.1161/HYPERTENSIONAHA.109.149690

Gant, 1973, A study of angiotensin II pressor response throughout primigravid pregnancy, J. Clin. Invest., 52, 2682, 10.1172/JCI107462

Saxena, 2010, Increased sensitivity to angiotensin II is present postpartum in women with a history of hypertensive pregnancy, Hypertension, 55, 1239, 10.1161/HYPERTENSIONAHA.109.147595

AbdAlla, 2001, Increased At1 receptor heterodimers in preeclampsia mediate enhanced angiotensin II responsiveness, Nat. Med., 7, 1003, 10.1038/nm0901-1003

Mishra, 2011, Mechanisms of enhanced vascular reactivity in preeclampsia, Hypertension, 58, 867, 10.1161/HYPERTENSIONAHA.111.176602

Verdonk, 2012, Reactive oxygen species and angiotensin ii response in human omental arteries: What about tachyphylaxis?, Hypertension, 59, e16, 10.1161/HYPERTENSIONAHA.111.187187

Wallukat, 1999, Patients with preeclampsia develop agonistic autoantibodies against the angiotensin At1 receptor, J. Clin. Invest., 103, 945, 10.1172/JCI4106

Siddiqui, 2010, Angiotensin receptor agonistic autoantibody is highly prevalent in preeclampsia correlation with disease severity, Hypertension, 55, 386, 10.1161/HYPERTENSIONAHA.109.140061

Dechend, 2004, At1 receptor agonistic antibodies, hypertension, and preeclampsia, Semin. Nephrol., 24, 571, 10.1016/j.semnephrol.2004.07.006

Herse, 2009, Prevalence of agonistic autoantibodies against the angiotensin II type 1 receptor and soluble fms-like tyrosine kinase 1 in a gestational age-matched case study, Hypertension, 53, 393, 10.1161/HYPERTENSIONAHA.108.124115

Stepan, 2007, Is parvovirus b19 the cause for autoimmunity against the angiotensin II type receptor?, J. Reprod. Immunol., 73, 130, 10.1016/j.jri.2006.08.084

Langer, 1998, Plasma active renin, angiotensin I, and angiotensin II during pregnancy and in preeclampsia, Obstet. Gynecol., 91, 196, 10.1016/S0029-7844(97)00660-1

Bharadwaj, 2011, Angiotensin-converting enzyme 2 deficiency is associated with impaired gestational weight gain and fetal growth restriction, Hypertension, 58, 852, 10.1161/HYPERTENSIONAHA.111.179358

Sykes, 2013, Fetal sex and the circulating renin–angiotensin system during early gestation in women who later develop preeclampsia or gestational hypertension, J. Hum. Hypertens.

Machado, 2001, Mechanisms of angiotensin-(1–7)-induced inhibition of angiogenesis, Am. J. Physiol. Regul. Integr. Comp. Physiol., 280, R994, 10.1152/ajpregu.2001.280.4.R994

Gennari-Moser, 2011, Regulation of placental growth by aldosterone and cortisol, Endocrinology, 152, 263, 10.1210/en.2010-0525

Batenburg, 2012, Angiotensin II–aldosterone interaction in human coronary microarteries involves GPR30, EGFR, and endothelial NO synthase, Cardiovasc. Res., 94, 136, 10.1093/cvr/cvs016

Escher, 2009, High aldosterone-to-renin variants of cyp11b2 and pregnancy outcome, Nephrol. Dial. Transplant., 24, 1870, 10.1093/ndt/gfn763

Gallery, 1984, Fall in blood pressure in response to volume expansion in pregnancy-associated hypertension (pre-eclampsia): why does it occur?, J. Hypertens., 2, 177, 10.1097/00004872-198404000-00009

Farese, 2006, Blood pressure reduction in pregnancy by sodium chloride, Nephrol. Dial. Transplant., 21, 1984, 10.1093/ndt/gfl106

Gennari-Moser, 2013, Vascular endothelial growth factor-a and aldosterone relevance to normal pregnancy and preeclampsia, Hypertension, 61, 1111, 10.1161/HYPERTENSIONAHA.111.00575

Siddiqui, 2013, Angiotensin receptor agonistic autoantibody-mediated soluble fms-like tyrosine kinase-1 induction contributes to impaired adrenal vasculature and decreased aldosterone production in preeclampsia, Hypertension, 61, 472, 10.1161/HYPERTENSIONAHA.111.00157

Buhl, 2012, Urinary plasmin activates collecting duct enac current in preeclampsia, Hypertension, 60, 1346, 10.1161/HYPERTENSIONAHA.112.198879

Brown, 1992, Renin–aldosterone relationships in pregnancy-induced hypertension, Am. J. Hypertens., 5, 366, 10.1093/ajh/5.6.366

Seva-Pessôa, 2012, Key developments in renin–angiotensin–aldosterone system inhibition, Nat. Rev. Nephrol., 9, 26, 10.1038/nrneph.2012.249

Verdonk, 2011, Do angiotensin II type 2 receptors mediate the enhanced angiotensin II constrictor response in pre-eclampsia?, Hypertension, 58, E40

Florijn, 1991, Plasma immunoreactive endothelin-1 in pregnant women with and without pre-eclampsia, J. Cardiovasc. Pharmacol., 17, S446, 10.1097/00005344-199100177-00128

Krop, 2013, The (pro)renin receptor. A decade of research: what have we learned?, Pflügers Arch., 465, 87, 10.1007/s00424-012-1105-z

van den Heuvel, 2011, Urinary renin, but not angiotensinogen or aldosterone, reflects the renal renin–angiotensin–aldosterone system activity and the efficacy of renin–angiotensin–aldosterone system blockade in the kidney, J. Hypertens., 29, 2147, 10.1097/HJH.0b013e32834bbcbf

Persson, 2013, Urinary renin and angiotensinogen in type 2 diabetes: added value beyond urinary albumin?, J. Hypertens., 31, 1646, 10.1097/HJH.0b013e328362217c