Renin-Angiotensin-Aldosterone System in the Pathogenesis of Pregnancy-Induced Hypertension

Summary

Hypertension occurs in 7–10% of pregnant women. Despite the continuous development of medicine, it is still an important risk factor for perinatal mortality of both mothers and fetuses. Pregnant women with hypertension are at greater risk of complications such as: placental abruption, cerebral and cardiac incidents, multiorgan failure, and disseminated intravascular coagulation. The aim of this review was to discuss multilevel disorders of the renin-angiotensin-aldosterone system in the etiopathogenesis of pregnancy-induced hypertension.

Key words

renin - angiotensin - aldosterone - pregnancy - hypertension - preeclampsia

• References

• 1 Naderi S, Tsai SA, Khandelwal A. Hypertensive disorders of pregnancy. Curr Atheroscler Rep 2017; 19: 15 doi:10.1007/s11883-017-0648-z
• 2 Maksym M, Madej P, Lemm MA. Etiopathogenesis of hypertension in pregnant women. Ann Acad Med. Siles (online) 2015; 69-75 [Polish]
• 3 Rapacz A, Filipek B. Nadciśnienie tętnicze w ciąży [Hypertension in pregnancy]. Terapia i Leki 2009; 65: 581-585 [Polish]
• 4 Helmo FR, Lopes AMM, Carneiro ACDM. et al. Angiogenic and antiangiogenic factors in preeclampsia. Pathol Res Pract. 2017;
• 5 Ngene NC, Moodley J. Role of angiogenic factors in the pathogenesis and management of pre-eclampsia. Int J Gynaecol Obstet. 2017;
• 6 Grafka A, Łopucki M, Pęksa B. et al. PLGF and sFlt-1 in clinical diagnosis of preeclampsia. Diag Lab 2014; 50: 339-344 [Polish]
• 7 Irani RA, Xia Y. Renin angiotensin signaling in normal pregnancy and preeclampsia. Semin Nephrol 2011; 31: 47-58
• 8 Verdonk K, Visser W, Van Den Meiracker AH. et al. The renin-angiotensin-aldosterone system in pre-eclampsia: the delicate balance between good and bad. Clin Sci (Lond) 2014; 126: 537-544
• 9 Gennari-Moser C, Khankin EV, Escher G. et al. Vascular endothelial growth factor-A and aldosterone: Relevance to normal pregnancy and preeclampsia. Hypertension 2013; 61: 1111-1117
• 10 Kuśmierska-Urban K, Rytlewski K, Reroń A. Selected polymorphisms of Renin-Angiotensin System in the pathology of hypertensive disorders of pregnancy. Ginekol Pol. 2013; 84: 214-218 [Polish]
• 11 Chaszczewska-Markowska M, Sagan M, Bogunia-Kubik K. The renin-angiotensin-aldosterone system (RAAS) – physiology and molecular mechanisms of functioning. Postepy Hig Med Dosw (Online) 2016; 70: 917-927
• 12 Eisele N, Albrecht C, Mistry HD. et al. Placental expression of the angiogenic placental growth factor is stimulated by both aldosterone and simulated starvation. Placenta 2016; 40: 18-24
• 13 Brown MA, Nicholson E, Gallery ED. Sodium-renin-aldosterone relations in normal and hypertensive pregnancy. Br J Obstet Gynaecol 1988; 95: 1237-1246
• 14 Merrill DC, Karoly M, Chen K. et al. Angiotensin-(1-7) in normal and preeclamptic pregnancy. Endocrine 2002; 18: 239-245
• 15 Verdonk K, Saleh L, Smilde JE. et al. A key role for endothelin-1 in the pathogenesis of preeclampsia and the associated suppression of the renin-angiotensin-aldosterone system. J Hypertens 2015; 33 (Suppl. 01) e110
• 16 Verdonk K, Saleh L, Lankhorst S. et al. Association studies suggest a key role for endothelin-1 in the pathogenesis of preeclampsia and the accompanying renin-angiotensin-aldosterone system suppression. Hypertension 2015; 65: 1316-1323
• 17 Herse F, Dechend R, Harsem NK. et al. Dysregulation of the circulating and tissue-based renin-angiotensin system in preeclampsia. Hypertension 2007; 49: 604-611
• 18 Miyamoto S, Shimokawa H, Sumioki H. et al. Circadian rhythm of plasma atrial natriuretic peptide, aldosterone, and blood pressure during the third trimester in normal and preeclamptic pregnancies. Am J Obstet Gynecol 1988; 158: 393-399
• 19 Bogacz A, Bartkowiak-Wieczorek J, Procyk D. et al. Analysis of the gene polymorphism of aldosterone synthase (CYP11B2) and atrial natriuretic peptide (ANP) in women with preeclampsia. Eur J Obstet Gynecol Reprod Biol 2016; 197: 11-15
• 20 AbdAlla S, Lother H, el Massiery A. et al. Increased AT(1) receptor heterodimers in preeclampsia mediate enhanced angiotensin II responsiveness. Nat Med 2001; 7: 1003-1009
• 21 Aggarwal S, Makris A, Hennessy A. Linking the old and new – do angiotensin II type 1 receptor antibodies provide the missing link in the pathophysiology of preeclampsia?. Hypertens Pregnancy 2015; 34: 369-382
• 22 Siddiqui AH, Irani RA, Blackwell SC. et al. Angiotensin receptor agonistic autoantibody is highly prevalent in preeclampsia: correlation with disease severity. Hypertension 2010; 55: 386-393
• 23 Wallukat G, Homuth V, Fischer T. et al. Patients with preeclampsia develop agonistic autoantibodies against the angiotensin AT1 receptor. J Clin Invest 1999; 103: 945-952
• 24 Siddiqui AH, Irani RA, Zhang W. et al. Angiotensin receptor agonistic autoantibody-mediated soluble fms-like tyrosine kinase-1 induction contributes to impaired adrenal vasculature and decreased aldosterone production in preeclampsia. Hypertension 2013; 61: 472-429
• 25 Zhou CC, Zhang Y, Irani RA. et al. Angiotensin receptor agonistic autoantibodies induce pre-eclampsia in pregnant mice. Nat Med 2008; 14: 855-862
• 26 Dechend R, Müller DN, Wallukat G. et al. AT1 receptor agonistic antibodies, hypertension, and preeclampsia. Semin Nephrol 2004; 24: 571-579
• 27 Dechend R, Homuth V, Wallukat G. et al. AT(1) receptor agonistic antibodies from preeclamptic patients cause vascular cells to express tissue factor. Circulation 2000; 101: 2382-2387
• 28 Raijmakers MT, Dechend R, Poston L. Oxidative stress and preeclampsia: Rationale for antioxidant clinical trials. Hypertension 2004; 44: 374-380
• 29 Xia Y, Wen H, Bobst S. et al. Maternal autoantibodies from preeclamptic patients activate angiotensin receptors on human trophoblast cells. J Soc Gynecol Investig 2003; 10: 82-93
• 30 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 signaling. Hypertension 2008; 51: 1010-1019
• 31 Ferrara N, Chen H, Davis-Smyth T. et al. Vascular endothelial growth factor is essential for corpus luteum angiogenesis. Nat Med 1998; 4: 336-340
• 32 Roeckl W, Hecht D, Sztajer H. et al. Differential binding characteristics and cellular inhibition by soluble VEGF receptors 1 and 2. Exp Cell Res 1998; 241: 161-170
• 33 Rana S, Powe CE, Salahuddin S. et al. Angiogenic factors and the risk of adverse outcomes in women with suspected preeclampsia. Circulation 2012; 125: 911-919
• 34 Verlohren S, Stepan H, Dechend R. Angiogenic growth factors in the diagnosis and prediction of pre-eclampsia. Clin Sci (Lond) 2012; 122: 43-52
• 35 Verlohren S, Herraiz I, Lapaire O. et al. The sFlt-1/PlGF ratio in different types of hypertensive pregnancy disorders and its prognostic potential in preeclamptic patients. Am J Obstet Gynecol 2012; 206 (01) 58e1-58e8
• 36 Yang J, Li L, Shang JY. et al. Angiotensin II type 1 receptor autoantibody as a novel regulator of aldosterone independent of preeclampsia. J Hypertens. 2015; 33: 1046-1056
• 37 Charkiewicz K, Jasinska E, Goscik J. et al. Angiogenic factor screening in women with mild preeclampsia – New and significant proteins in plasma. Cytokine 2017;
• 38 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-1. Hypertension 2009; 54: 905-909
• 39 Bakrania B, Duncan J, Warrington JP. et al. The endothelin type A receptor as a potential therapeutic target in preeclampsia. Int J Mol Sci 2017; 18 pii: E522
• 40 Saleh L, Verdonk K, Visser W. et al. The emerging role of endothelin-1 in the pathogenesis of pre-eclampsia. Ther Adv Cardiovasc Dis 2016; 10: 282-293
• 42 Aggarwal PK, Chandel N, Jain V. et al. The relationship between circulating endothelin-1, soluble fms-like tyrosine kinase-1 and soluble endoglin in preeclampsia. J Hum Hypertens 2012; 26: 236-341
• 42 Lei J, Li Y, Zhang S. et al. The prognostic role of angiotensin ii type 1 receptor autoantibody in non-gravid hypertension and pre-eclampsia: A meta-analysis and our studies. Medicine (Baltimore) 2016; 95: e3494
• 43 Kløverpris S, Skov LL, Glerup S. et al. 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. 2013; 449: 209-217
• 44 Weyer K, Glerup S. Placental regulation of peptide hormone and growth factor activity by proMBP. Biol Reprod. 2011; 84: 1077-1086
• 45 Buhl KB, Friis UG, Svenningsen P. et al. Urinary plasmin activates collecting duct ENaC current in preeclampsia. Hypertension 2012; 60: 1346-1351
• 46 Zhang XQ, Varner M, Dizon-Townson D. et al. A molecular variant of angiotensinogen is associated with idiopathic intrauterine growth restriction. Obstet Gynecol 2003; 101: 237-242
• 47 Zafarmand MH, Franx A, Sabour S. et al. The M235T variant of the angiotensinogen gene is related to development of self-reported hypertension during pregnancy: the Prospect-EPIC cohort study. Hypertens Res 2008; 31: 1299-1305
• 48 Zafarmand MH, Nijdam ME, Franx A. et al. The angiotensinogen gene M235T polymorphism and development of preeclampsia/eclampsia: A meta-analysis and meta-regression of observational studies. J Hypertens 2008; 26: 1726-1734
• 49 Li H, Ma Y, Fu Q. et al. Angiotensin-converting enzyme insertion/deletion (ACE I/D) and angiotensin II type 1 receptor (AT1R) gene polymorphism and its association with preeclampsia in Chinese women. Hypertens Pregnancy 2007; 26: 293-301