International Journal of Endocrinology and Metabolism

Published by: Kowsar

Hormones and Hemodynamics in Pregnancy

Oleksandra Tkachenko 1 , Dmitry Shchekochikhin 1 and Robert W. Schrier 1 , *
Authors Information
1 Division of Renal Diseases and Hypertension, University of Colorado Denver, Denver, Colorado, USA
Article information
  • International Journal of Endocrinology and Metabolism: April 01, 2014, 12 (2); e14098
  • Published Online: April 1, 2014
  • Article Type: Review Article
  • Received: September 18, 2013
  • Revised: October 15, 2013
  • Accepted: December 10, 2013
  • DOI: 10.5812/ijem.14098

To Cite: Tkachenko O, Shchekochikhin D, W. Schrier R. Hormones and Hemodynamics in Pregnancy, Int J Endocrinol Metab. 2014 ; 12(2):e14098. doi: 10.5812/ijem.14098.

Copyright © 2014, Research Institute For Endocrine Sciences and Iran Endocrine Society. This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License ( which permits copy and redistribute the material just in noncommercial usages, provided the original work is properly cited.
1. Context
2. Evidence Acquisition
3. Results
4. Conclusions
  • 1. Chapman AB, Abraham WT, Zamudio S, Coffin C, Merouani A, Young D, et al. Temporal relationships between hormonal and hemodynamic changes in early human pregnancy. Kidney Int. 1998; 54(6): 2056-63[DOI][PubMed]
  • 2. van Buul EJ, Steegers EA, Jongsma HW, Eskes TK, Thomas CM, Hein PR. Haematological and biochemical profile of uncomplicated pregnancy in nulliparous women; a longitudinal study. Neth J Med. 1995; 46(2): 73-85[PubMed]
  • 3. Hytten F. Blood volume changes in normal pregnancy. Clin Haematol. 1985; 14(3): 601-12[PubMed]
  • 4. Lukaski HC, Siders WA, Nielsen EJ, Hall CB. Total body water in pregnancy: assessment by using bioelectrical impedance. Am J Clin Nutr. 1994; 59(3): 578-85[PubMed]
  • 5. Wilson M, Morganti AA, Zervoudakis I, Letcher RL, Romney BM, Von Oeyon P, et al. Blood pressure, the renin-aldosterone system and sex steroids throughout normal pregnancy. Am J Med. 1980; 68(1): 97-104[PubMed]
  • 6. Sealey JE, Itskovitz-Eldor J, Rubattu S, James GD, August P, Thaler I, et al. Estradiol- and progesterone-related increases in the renin-aldosterone system: studies during ovarian stimulation and early pregnancy. J Clin Endocrinol Metab. 1994; 79(1): 258-64[DOI][PubMed]
  • 7. Paller MS, Gregorini G, Ferris TF. Pressor responsiveness in pseudopregnant and pregnant rats: role of maternal factors. Am J Physiol. 1989; 257(4 Pt 2)-71[PubMed]
  • 8. Chapman AB, Zamudio S, Woodmansee W, Merouani A, Osorio F, Johnson A, et al. Systemic and renal hemodynamic changes in the luteal phase of the menstrual cycle mimic early pregnancy. Am J Physiol. 1997; 273(5 Pt 2)-82[PubMed]
  • 9. Robb AO, Mills NL, Din JN, Smith IB, Paterson F, Newby DE, et al. Influence of the menstrual cycle, pregnancy, and preeclampsia on arterial stiffness. Hypertension. 2009; 53(6): 952-8[DOI][PubMed]
  • 10. Balasch J, Arroyo V, Carmona F, Llach J, Jimenez W, Pare JC, et al. Severe ovarian hyperstimulation syndrome: role of peripheral vasodilation. Fertil Steril. 1991; 56(6): 1077-83[PubMed]
  • 11. Hytten FE, Robertson EG. Maternal water metabolism in pregnancy. Proc R Soc Med. 1971; 64(10): 1072[PubMed]
  • 12. Newman RL. Serum electrolytes in pregnancy, parturition, and puerperium. Obstet Gynecol. 1957; 10(1): 51-5[PubMed]
  • 13. Lindheimer MD, Davison JM. Osmoregulation, the secretion of arginine vasopressin and its metabolism during pregnancy. Eur J Endocrinol. 1995; 132(2): 133-43[PubMed]
  • 14. Schrier RW, Briner VA. Peripheral arterial vasodilation hypothesis of sodium and water retention in pregnancy: implications for pathogenesis of preeclampsia-eclampsia. Obstet Gynecol. 1991; 77(4): 632-9[PubMed]
  • 15. Schrier RW. Body fluid volume regulation in health and disease: a unifying hypothesis. Ann Intern Med. 1990; 113(2): 155-9[PubMed]
  • 16. Robson SC, Hunter S, Boys RJ, Dunlop W. Serial study of factors influencing changes in cardiac output during human pregnancy. Am J Physiol. 1989; 256(4 Pt 2)-5[PubMed]
  • 17. Schrier RW. Pathogenesis of sodium and water retention in high-output and low-output cardiac failure, nephrotic syndrome, cirrhosis, and pregnancy (2). N Engl J Med. 1988; 319(17): 1127-34[DOI][PubMed]
  • 18. August P, Lenz T, Ales KL, Druzin ML, Edersheim TG, Hutson JM, et al. Longitudinal study of the renin-angiotensin-aldosterone system in hypertensive pregnant women: deviations related to the development of superimposed preeclampsia. Am J Obstet Gynecol. 1990; 163(5 Pt 1): 1612-21[PubMed]
  • 19. Davison JM. Renal haemodynamics and volume homeostasis in pregnancy. Scand J Clin Lab Invest Suppl. 1984; 169: 15-27[PubMed]
  • 20. Phippard AF, Horvath JS, Glynn EM, Garner MG, Fletcher PJ, Duggin GG, et al. Circulatory adaptation to pregnancy--serial studies of haemodynamics, blood volume, renin and aldosterone in the baboon (Papio hamadryas). J Hypertens. 1986; 4(6): 773-9[PubMed]
  • 21. Gonzalez-Campoy JM, Romero JC, Knox FG. Escape from the sodium-retaining effects of mineralocorticoids: role of ANF and intrarenal hormone systems. Kidney Int. 1989; 35(3): 767-77[PubMed]
  • 22. Knight S, Snellen H, Humphreys M, Baylis C. Increased renal phosphodiesterase-5 activity mediates the blunted natriuretic response to ANP in the pregnant rat. Am J Physiol Renal Physiol. 2007; 292(2)-9[DOI][PubMed]
  • 23. Boron WF, Boulpaep EL. Medical physiology. 2005;
  • 24. Dhanjal MK, Owen EP, Anthony JA, Davidson JS, Rayner BL. Association of pre-eclampsia with the R563Q mutation of the beta-subunit of the epithelial sodium channel. BJOG. 2006; 113(5): 595-8[DOI][PubMed]
  • 25. Salas SP, Giacaman A, Vio CP. Renal and hormonal effects of water deprivation in late-term pregnant rats. Hypertension. 2004; 44(3): 334-9[DOI][PubMed]
  • 26. Pike RL. Soidum requirement of the rat during pregnancy. Perspect Nephrol Hypertens. 1976; 5: 207-15[PubMed]
  • 27. Salas SP, Marshall G, Gutierrez BL, Rosso P. Time course of maternal plasma volume and hormonal changes in women with preeclampsia or fetal growth restriction. Hypertension. 2006; 47(2): 203-8[DOI][PubMed]
  • 28. Tamas P, Worgall S, Sulyok E, Rascher W. Renal electrolyte and water handling in normal pregnancy: possible role of endothelin-1. Eur J Obstet Gynecol Reprod Biol. 1994; 55(2): 89-95[PubMed]
  • 29. Rosenbloom AA, Sack J, Fisher DA. The circulating vasopressinase of pregnancy: species comparison with radioimmunoassay. Am J Obstet Gynecol. 1975; 121(3): 316-20[PubMed]
  • 30. Davison JM, Sheills EA, Barron WM, Robinson AG, Lindheimer MD. Changes in the metabolic clearance of vasopressin and in plasma vasopressinase throughout human pregnancy. J Clin Invest. 1989; 83(4): 1313-8[DOI][PubMed]
  • 31. Durr JA, Stamoutsos B, Lindheimer MD. Osmoregulation during pregnancy in the rat. Evidence for resetting of the threshold for vasopressin secretion during gestation. J Clin Invest. 1981; 68(2): 337-46[PubMed]
  • 32. Davison JM, Shiells EA, Philips PR, Lindheimer MD. Serial evaluation of vasopressin release and thirst in human pregnancy. Role of human chorionic gonadotrophin in the osmoregulatory changes of gestation. J Clin Invest. 1988; 81(3): 798-806[DOI][PubMed]
  • 33. Davison JM, Gilmore EA, Durr J, Robertson GL, Lindheimer MD. Altered osmotic thresholds for vasopressin secretion and thirst in human pregnancy. Am J Physiol. 1984; 246(1 Pt 2)-9[PubMed]
  • 34. Ohara M, Martin PY, Xu DL, St John J, Pattison TA, Kim JK, et al. Upregulation of aquaporin 2 water channel expression in pregnant rats. J Clin Invest. 1998; 101(5): 1076-83[DOI][PubMed]
  • 35. Xu DL, Martin PY, St John J, Tsai P, Summer SN, Ohara M, et al. Upregulation of endothelial and neuronal constitutive nitric oxide synthase in pregnant rats. Am J Physiol. 1996; 271(6 Pt 2)-45[PubMed]
  • 36. Fushimi K, Uchida S, Hara Y, Hirata Y, Marumo F, Sasaki S. Cloning and expression of apical membrane water channel of rat kidney collecting tubule. Nature. 1993; 361(6412): 549-52[DOI][PubMed]
  • 37. Asahina Y, Izumi N, Enomoto N, Sasaki S, Fushimi K, Marumo F, et al. Increased gene expression of water channel in cirrhotic rat kidneys. Hepatology. 1995; 21(1): 169-73[PubMed]
  • 38. Xu DL, Martin PY, Ohara M, St John J, Pattison T, Meng X, et al. Upregulation of aquaporin-2 water channel expression in chronic heart failure rat. J Clin Invest. 1997; 99(7): 1500-5[DOI][PubMed]
  • 39. Buemi M, D'Anna R, Di Pasquale G, Floccari F, Ruello A, Aloisi C, et al. Urinary excretion of aquaporin-2 water channel during pregnancy. Cell Physiol Biochem. 2001; 11(4): 203-8[PubMed]
  • 40. Conrad KP, Debrah DO, Novak J, Danielson LA, Shroff SG. Relaxin modifies systemic arterial resistance and compliance in conscious, nonpregnant rats. Endocrinology. 2004; 145(7): 3289-96[DOI][PubMed]
  • 41. Debrah DO, Novak J, Matthews JE, Ramirez RJ, Shroff SG, Conrad KP. Relaxin is essential for systemic vasodilation and increased global arterial compliance during early pregnancy in conscious rats. Endocrinology. 2006; 147(11): 5126-31[DOI][PubMed]
  • 42. Danielson LA, Kercher LJ, Conrad KP. Impact of gender and endothelin on renal vasodilation and hyperfiltration induced by relaxin in conscious rats. Am J Physiol Regul Integr Comp Physiol. 2000; 279(4)-304[PubMed]
  • 43. Dschietzig T, Teichman S, Unemori E, Wood S, Boehmer J, Richter C, et al. Intravenous recombinant human relaxin in compensated heart failure: a safety, tolerability, and pharmacodynamic trial. J Card Fail. 2009; 15(3): 182-90[DOI][PubMed]
  • 44. Smith MC, Danielson LA, Conrad KP, Davison JM. Influence of recombinant human relaxin on renal hemodynamics in healthy volunteers. J Am Soc Nephrol. 2006; 17(11): 3192-7[DOI][PubMed]
  • 45. Palejwala S, Stein DE, Weiss G, Monia BP, Tortoriello D, Goldsmith LT. Relaxin positively regulates matrix metalloproteinase expression in human lower uterine segment fibroblasts using a tyrosine kinase signaling pathway. Endocrinology. 2001; 142(8): 3405-13[DOI][PubMed]
  • 46. Teichman SL, Unemori E, Dschietzig T, Conrad K, Voors AA, Teerlink JR, et al. Relaxin, a pleiotropic vasodilator for the treatment of heart failure. Heart Fail Rev. 2009; 14(4): 321-9[DOI][PubMed]
  • 47. McGuane JT, Danielson LA, Debrah JE, Rubin JP, Novak J, Conrad KP. Angiogenic growth factors are new and essential players in the sustained relaxin vasodilatory pathway in rodents and humans. Hypertension. 2011; 57(6): 1151-60[DOI][PubMed]
  • 48. Fernandez-Patron C, Radomski MW, Davidge ST. Vascular matrix metalloproteinase-2 cleaves big endothelin-1 yielding a novel vasoconstrictor. Circ Res. 1999; 85(10): 906-11[PubMed]
  • 49. Jeyabalan A, Novak J, Danielson LA, Kerchner LJ, Opett SL, Conrad KP. Essential role for vascular gelatinase activity in relaxin-induced renal vasodilation, hyperfiltration, and reduced myogenic reactivity of small arteries. Circ Res. 2003; 93(12): 1249-57[DOI][PubMed]
  • 50. Weiner C, Martinez E, Zhu LK, Ghodsi A, Chestnut D. In vitro release of endothelium-derived relaxing factor by acetylcholine is increased during the guinea pig pregnancy. Am J Obstet Gynecol. 1989; 161(6 Pt 1): 1599-605[PubMed]
  • 51. Conrad KP, Joffe GM, Kruszyna H, Kruszyna R, Rochelle LG, Smith RP, et al. Identification of increased nitric oxide biosynthesis during pregnancy in rats. FASEB J. 1993; 7(6): 566-71[PubMed]
  • 52. Weiner CP, Knowles RG, Moncada S. Induction of nitric oxide synthases early in pregnancy. Am J Obstet Gynecol. 1994; 171(3): 838-43[PubMed]
  • 53. Kassab S, Miller MT, Hester R, Novak J, Granger JP. Systemic hemodynamics and regional blood flow during chronic nitric oxide synthesis inhibition in pregnant rats. Hypertension. 1998; 31(1 Pt 2): 315-20[PubMed]
  • 54. Cadnapaphornchai MA, Ohara M, Morris KG, Jr., Knotek M, Rogachev B, Ladtkow T, et al. Chronic NOS inhibition reverses systemic vasodilation and glomerular hyperfiltration in pregnancy. Am J Physiol Renal Physiol. 2001; 280(4)-8[PubMed]
  • 55. Osheroff PL, Phillips HS. Autoradiographic localization of relaxin binding sites in rat brain. Proc Natl Acad Sci U S A. 1991; 88(15): 6413-7[PubMed]
  • 56. McKinley MJ, Colvill LM, Giles ME, Oldfield BJ. Distribution of Fos-immunoreactivity in rat brain following a dipsogenic dose of captopril and effects of angiotensin receptor blockade. Brain Res. 1997; 747(1): 43-51[PubMed]
  • 57. Summerlee AJ, Robertson GF. Central administration of porcine relaxin stimulates drinking behaviour in rats: an effect mediated by central angiotensin II. Endocrine. 1995; 3(5): 377-81[DOI][PubMed]
  • 58. Mumford AD, Parry LJ, Summerlee AJ. Lesion of the subfornical organ affects the haemotensive response to centrally administered relaxin in anaesthetized rats. J Endocrinol. 1989; 122(3): 747-55[PubMed]
  • 59. Weisinger RS, Burns P, Eddie LW, Wintour EM. Relaxin alters the plasma osmolality-arginine vasopressin relationship in the rat. J Endocrinol. 1993; 137(3): 505-10[PubMed]
  • 60. Danielson LA, Sherwood OD, Conrad KP. Relaxin is a potent renal vasodilator in conscious rats. J Clin Invest. 1999; 103(4): 525-33[DOI][PubMed]
  • 61. Smith MC, Murdoch AP, Danielson LA, Conrad KP, Davison JM. Relaxin has a role in establishing a renal response in pregnancy. Fertil Steril. 2006; 86(1): 253-5[DOI][PubMed]
  • 62. Johnson MR, Brooks AA, Steer PJ. The role of relaxin in the pregnancy associated reduction in plasma osmolality. Hum Reprod. 1996; 11(5): 1105-8[PubMed]
  • 63. Sunn N, Egli M, Burazin TC, Burns P, Colvill L, Davern P, et al. Circulating relaxin acts on subfornical organ neurons to stimulate water drinking in the rat. Proc Natl Acad Sci U S A. 2002; 99(3): 1701-6[DOI][PubMed]
  • 64. Sinnayah P, Burns P, Wade JD, Weisinger RS, McKinley MJ. Water drinking in rats resulting from intravenous relaxin and its modification by other dipsogenic factors. Endocrinology. 1999; 140(11): 5082-6[DOI][PubMed]
  • 65. Geddes BJ, Parry LJ, Summerlee AJ. Brain angiotensin-II partially mediates the effects of relaxin on vasopressin and oxytocin release in anesthetized rats. Endocrinology. 1994; 134(3): 1188-92[DOI][PubMed]
  • 66. Gant NF, Worley RJ, Everett RB, MacDonald PC. Control of vascular responsiveness during human pregnancy. Kidney Int. 1980; 18(2): 253-8[PubMed]
  • 67. Baker PN, Broughton Pipkin F, Symonds EM. Platelet angiotensin II binding and plasma renin concentration, plasma renin substrate and plasma angiotensin II in human pregnancy. Clin Sci (Lond). 1990; 79(4): 403-8[PubMed]
  • 68. LARAGH JH. Hormones and the Pathogenesis of Congestive Heart Failure:Vasopressin, Aldosterone, and Angiotensin II: Further Evidence for Renal-Adrenal Interaction from Studies in Hypertension and in Cirrhosis. Circulation. 1962; 25(6): 1015-23[DOI]
  • 69. Duley L. The global impact of pre-eclampsia and eclampsia. Semin Perinatol. 2009; 33(3): 130-7[DOI][PubMed]
  • 70. Dennis AT, Castro J, Carr C, Simmons S, Permezel M, Royse C. Haemodynamics in women with untreated pre-eclampsia. Anaesthesia. 2012; 67(10): 1105-18[DOI][PubMed]
  • 71. Visser W, Wallenburg HC. Central hemodynamic observations in untreated preeclamptic patients. Hypertension. 1991; 17(6 Pt 2): 1072-7[PubMed]
  • 72. Maynard SE, Min JY, Merchan J, Lim KH, Li J, Mondal S, et al. Excess placental soluble fms-like tyrosine kinase 1 (sFlt1) may contribute to endothelial dysfunction, hypertension, and proteinuria in preeclampsia. J Clin Invest. 2003; 111(5): 649-58[DOI][PubMed]
  • 73. Venkatesha S, Toporsian M, Lam C, Hanai J, Mammoto T, Kim YM, et al. Soluble endoglin contributes to the pathogenesis of preeclampsia. Nat Med. 2006; 12(6): 642-9[DOI][PubMed]
  • 74. Gant NF, Daley GL, Chand S, Whalley PJ, MacDonald PC. A study of angiotensin II pressor response throughout primigravid pregnancy. J Clin Invest. 1973; 52(11): 2682-9[DOI][PubMed]
  • 75. AbdAlla S, Lother H, el Massiery A, Quitterer U. Increased AT(1) receptor heterodimers in preeclampsia mediate enhanced angiotensin II responsiveness. Nat Med. 2001; 7(9): 1003-9[DOI][PubMed]
  • 76. Wallukat G, Homuth V, Fischer T, Lindschau C, Horstkamp B, Jupner A, et al. Patients with preeclampsia develop agonistic autoantibodies against the angiotensin AT1 receptor. J Clin Invest. 1999; 103(7): 945-52[DOI][PubMed]
  • 77. Merrill DC, Karoly M, Chen K, Ferrario CM, Brosnihan KB. Angiotensin-(1-7) in normal and preeclamptic pregnancy. Endocrine. 2002; 18(3): 239-45[DOI][PubMed]
  • 78. Irani RA, Xia Y. Renin angiotensin signaling in normal pregnancy and preeclampsia. Semin Nephrol. 2011; 31(1): 47-58[DOI][PubMed]
  • 79. Bohrer MP, Deen WM, Robertson CR, Brenner BM. Mechanism of angiotensin II-induced proteinuria in the rat. Am J Physiol. 1977; 233(1)-21[PubMed]
  • 80. Axelsson J, Rippe A, Oberg CM, Rippe B. Rapid, dynamic changes in glomerular permeability to macromolecules during systemic angiotensin II (ANG II) infusion in rats. Am J Physiol Renal Physiol. 2012; 303(6)-9[DOI][PubMed]
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