1932

Abstract

Maternal cardiovascular changes during pregnancy include an expansion of plasma volume, increased cardiac output, decreased peripheral resistance, and increased uteroplacental blood flow. These adaptations facilitate the progressive increase in uteroplacental perfusion that is required for normal fetal growth and development, prevent the development of hypertension, and provide a reserve of blood in anticipation of the significant blood loss associated with parturition. Each woman's genotype and phenotype determine her ability to adapt in response to molecular signals that emanate from the fetoplacental unit. Here, we provide an overview of the major hemodynamic and cardiac changes and then consider regional changes in the splanchnic, renal, cerebral, and uterine circulations in terms of endothelial and vascular smooth muscle cell plasticity. Although consideration of gestational disease is beyond the scope of this review, aberrant signaling and/or maternal responsiveness contribute to the etiology of several common gestational diseases such as preeclampsia, intrauterine growth restriction, and gestational diabetes.

Loading

Article metrics loading...

/content/journals/10.1146/annurev-physiol-020518-114435
2019-02-10
2024-06-14
Loading full text...

Full text loading...

/deliver/fulltext/physiol/81/1/annurev-physiol-020518-114435.html?itemId=/content/journals/10.1146/annurev-physiol-020518-114435&mimeType=html&fmt=ahah

Literature Cited

  1. 1.  Torgersen KL, Curran CA 2006. A systematic approach to the physiologic adaptations of pregnancy. Crit. Care Nurs. Q. 29:2–19
    [Google Scholar]
  2. 2.  Chang J, Streitman D 2012. Physiologic adaptations to pregnancy. Neurol. Clin. 30:781–89
    [Google Scholar]
  3. 3.  Longo LD. 1983. Maternal blood volume and cardiac output during pregnancy: a hypothesis of endocrinologic control. Am. J. Physiol. 245:R720–29
    [Google Scholar]
  4. 4.  Robson SC, Hunter S, Boys RJ, Dunlop W 1989. Serial study of factors influencing changes in cardiac output during human pregnancy. Am. J. Physiol. 256:H1060–65
    [Google Scholar]
  5. 5.  Hunter S, Robson SC 1992. Adaptation of the maternal heart in pregnancy. Br. Heart J. 68:540–43
    [Google Scholar]
  6. 6.  Melchiorre K, Sharma R, Thilaganathan B 2012. Cardiac structure and function in normal pregnancy. Curr. Opin. Obstet. Gynecol. 24:413–21
    [Google Scholar]
  7. 7.  Place JC, Plano LR 2015. A case report of decreased fetal movement during fetomaternal hemorrhage. J. Obstet. Gynecol. Neonatal Nurs. 44:737–42
    [Google Scholar]
  8. 8.  Gandhi M, Martin SR 2015. Cardiac disease in pregnancy. Obstet. Gynecol. Clin. N. Am. 42:315–33
    [Google Scholar]
  9. 9.  Robson SC, Dunlop W 1992. Letters to the editors: When do cardiovascular parameters return to their preconception values?. Am. J. Obstet. Gynecol. 167:1479
    [Google Scholar]
  10. 10.  Osol G, Ko NL, Mandalà M 2017. Altered endothelial nitric oxide signaling as a paradigm for maternal vascular maladaptation in preeclampsia. Curr. Hypertens. Rep. 19:82
    [Google Scholar]
  11. 11.  Morton JS, Care AS, Davidge ST 2017. Mechanisms of uterine artery dysfunction in pregnancy complications. J. Cardiovasc. Pharmacol. 69:343–59
    [Google Scholar]
  12. 12.  Fournier T, Guibourdenche J, Evain-Brion D 2015. Review: hCGs: different sources of production, different glycoforms and functions. Placenta 36:Suppl. 1S60–65
    [Google Scholar]
  13. 13.  Hay DL, Lopata A 1988. Chorionic gonadotropin secretion by human embryos in vitro. J. Clin. Endocrinol. Metab. 67:1322–24
    [Google Scholar]
  14. 14.  Csapo AI, Pulkkinen MO, Wiest WG 1973. Effects of luteectomy and progesterone replacement therapy in early pregnant patients. Am. J. Obstet. Gynecol. 115:759–65
    [Google Scholar]
  15. 15.  Devroey P, Camus M, Palermo G, Smitz J, Van Waesberghe L et al. 1990. Placental production of estradiol and progesterone after oocyte donation in patients with primary ovarian failure. Am. J. Obstet. Gynecol. 162:66–70
    [Google Scholar]
  16. 16.  Levitz M, Young BK 1977. Estrogens in pregnancy. Vitam. Horm. 35:109–47
    [Google Scholar]
  17. 17.  O'Leary P, Boyne P, Flett P, Beilby J, James I 1991. Longitudinal assessment of changes in reproductive hormones during normal pregnancy. Clin. Chem. 37:667–72
    [Google Scholar]
  18. 18.  Zygmunt M, Herr F, Keller-Schoenwetter S, Kunzi-Rapp K, Münstedt K et al. 2002. Characterization of human chorionic gonadotropin as a novel angiogenic factor. J. Clin. Endocrinol. Metab. 87:5290–96
    [Google Scholar]
  19. 19.  Ambrus G, Rao CV 1994. Novel regulation of pregnant human myometrial smooth muscle cell gap junctions by human chorionic gonadotropin. Endocrinology 135:2772–79
    [Google Scholar]
  20. 20.  Bansal AS, Bora SA, Saso S, Smith JR, Johnson MR, Thum MY 2012. Mechanism of human chorionic gonadotrophin-mediated immunomodulation in pregnancy. Expert Rev. Clin. Immunol. 8:747–53
    [Google Scholar]
  21. 21.  Nwabuobi C, Arlier S, Schatz F, Guzeloglu-Kayisli O, Lockwood CJ, Kayisli UA 2017. hCG: biological functions and clinical applications. Int. J. Mol. Sci. 18:2037
    [Google Scholar]
  22. 22.  Berkane N, Liere P, Oudinet JP, Hertig A, Lefèvre G et al. 2017. From pregnancy to preeclampsia: a key role for estrogens. Endocr Rev 38:123–44
    [Google Scholar]
  23. 23.  Escobar JC, Patel SS, Beshay VE, Suzuki T, Carr BR 2011. The human placenta expresses CYP17 and generates androgens de novo. J. Clin. Endocrinol. Metab 96:1385–92
    [Google Scholar]
  24. 24.  Milewich L, MacDonald PC, Carr BR 1986. Estrogen 16α-hydroxylase activity in human fetal tissues. J. Clin. Endocrinol. Metab. 63:404–6
    [Google Scholar]
  25. 25.  Mueller JW, Gilligan LC, Idkowiak J, Arlt W, Foster PA 2015. The regulation of steroid action by sulfation and desulfation. Endocr Rev 36:526–63
    [Google Scholar]
  26. 26.  Hisaw FL. 1926. Experimental relaxation of the pubic ligament of the guinea pig. Proc. Soc. Exp. Biol. Med. 23:661–63
    [Google Scholar]
  27. 27.  Jelinic M, Marshall SA, Stewart D, Unemori E, Parry LJ, Leo CH 2018. Peptide hormone relaxin: from bench to bedside. Am. J. Physiol. Regul. Integr. Comp. Physiol. 314:R753–60
    [Google Scholar]
  28. 28.  Leo CH, Jelinic M, Ng HH, Marshall SA, Novak J et al. 2017. Vascular actions of relaxin: nitric oxide and beyond. Br. J. Pharmacol. 174:1002–14
    [Google Scholar]
  29. 29.  Conrad KP. 2011. Maternal vasodilation in pregnancy: the emerging role of relaxin. Am. J. Physiol. Regul. Integr. Comp. Physiol. 301:R267–75
    [Google Scholar]
  30. 30.  Stewart DR, Cragun JR, Boyers SP, Oi R, Overstreet JW, Lasley BL 1992. Serum relaxin concentrations in patients with out-of-phase endometrial biopsies. Fertil. Steril. 57:453–55
    [Google Scholar]
  31. 31.  Sherwood OD. 2004. Relaxin's physiological roles and other diverse actions. Endocr Rev 25:205–34
    [Google Scholar]
  32. 32.  Demir R, Kayisli UA, Seval Y, Celik-Ozenci C, Korgun ET et al. 2004. Sequential expression of VEGF and its receptors in human placental villi during very early pregnancy: differences between placental vasculogenesis and angiogenesis. Placenta 25:560–72
    [Google Scholar]
  33. 33.  Shiraishi S, Nakagawa K, Kinukawa N, Nakano H, Sueishi K 1996. Immunohistochemical localization of vascular endothelial growth factor in the human placenta. Placenta 17:111–21
    [Google Scholar]
  34. 34.  Valdés G, Corthorn J 2011. Challenges posed to the maternal circulation by pregnancy.. Integr. Blood Press. Control 4:45–53
    [Google Scholar]
  35. 35.  Sabapatha A, Gercel-Taylor C, Taylor DD 2006. Specific isolation of placenta-derived exosomes from the circulation of pregnant women and their immunoregulatory consequences. Am. J. Reprod. Immunol. 56:345–55
    [Google Scholar]
  36. 36.  Orozco AF, Lewis DE 2010. Flow cytometric analysis of circulating microparticles in plasma. Cytometry A 77:502–14
    [Google Scholar]
  37. 37.  Thery C, Zitvogel L, Amigorena S 2002. Exosomes: composition, biogenesis and function. Nat. Rev. Immunol. 2:569–79
    [Google Scholar]
  38. 38.  Bounds KR, Chiasson VL, Pan LJ, Gupta S, Chatterjee P 2017. MicroRNAs: new players in the pathobiology of preeclampsia. Front. Cardiovasc. Med. 4:60
    [Google Scholar]
  39. 39.  Jairajpuri DS, Malalla ZH, Mahmood N, Almawi WY 2017. Circulating microRNA expression as predictor of preeclampsia and its severity. Gene 627:543–48
    [Google Scholar]
  40. 40.  Bartolomei MS, Zemel S, Tilghman SM 1991. Parental imprinting of the mouse H19 gene. Nature 351:153–55
    [Google Scholar]
  41. 41.  Hirasawa R, Feil R 2010. Genomic imprinting and human disease. Essays Biochem 48:187–200
    [Google Scholar]
  42. 42.  Keniry A, Oxley D, Monnier P, Kyba M, Dandolo L et al. 2012. The H19 lincRNA is a developmental reservoir of miR-675 that suppresses growth and Igf1r. Nat. Cell Biol 14:659–65
    [Google Scholar]
  43. 43.  Morales-Prieto DM, Ospina-Prieto S, Schmidt A, Chaiwangyen W, Markert UR 2014. Elsevier Trophoblast Research Award Lecture: origin, evolution and future of placenta miRNAs. Placenta 35:Suppl. 1S39–45
    [Google Scholar]
  44. 44.  Ye W, Lv Q, Wong CK, Hu S, Fu C et al. 2008. The effect of central loops in miRNA:MRE duplexes on the efficiency of miRNA-mediated gene regulation. PLOS ONE 3:e1719
    [Google Scholar]
  45. 45.  Hu XQ, Dasgupta C, Xiao D, Huang X, Yang S, Zhang L 2017. MicroRNA-210 targets ten-eleven translocation methylcytosine dioxygenase 1 and suppresses pregnancy-mediated adaptation of large conductance Ca2+-activated K+ channel expression and function in ovine uterine arteries. Hypertension 70:601–12
    [Google Scholar]
  46. 46.  Fu Q, Levine BD 2009. Autonomic circulatory control during pregnancy in humans. Semin. Reprod. Med. 27:330–37
    [Google Scholar]
  47. 47.  Meyer MC, Osol G, McLaughlin M 1997. Flow decreases myogenic reactivity of mesenteric arteries from pregnant rats. J. Soc. Gynecol. Investig. 4:293–97
    [Google Scholar]
  48. 48.  Cockell AP, Poston L 1997. Flow-mediated vasodilatation is enhanced in normal pregnancy but reduced in preeclampsia. Hypertension 30:247–51
    [Google Scholar]
  49. 49.  Learmont JG, Cockell AP, Knock GA, Poston L 1996. Myogenic and flow-mediated responses in isolated mesenteric small arteries from pregnant and nonpregnant rats. Am. J. Obstet. Gynecol. 174:1631–36
    [Google Scholar]
  50. 50.  Veerareddy S, Cooke CL, Baker PN, Davidge ST 2002. Vascular adaptations to pregnancy in mice: effects on myogenic tone. Am. J. Physiol. Heart Circ. Physiol. 283:H2226–33
    [Google Scholar]
  51. 51.  Kenny LC, Baker PN, Kendall DA, Randall MD, Dunn WR 2002. The role of gap junctions in mediating endothelium-dependent responses to bradykinin in myometrial small arteries isolated from pregnant women. Br. J. Pharmacol. 136:1085–88
    [Google Scholar]
  52. 52.  Boeldt DS, Bird IM 2017. Vascular adaptation in pregnancy and endothelial dysfunction in preeclampsia. J. Endocrinol. 232:R27–44
    [Google Scholar]
  53. 53.  Carbillon L, Uzan M, Uzan S 2000. Pregnancy, vascular tone, and maternal hemodynamics: a crucial adaptation. Obstet. Gynecol. Surv. 55:574–81
    [Google Scholar]
  54. 54.  Kim TH, Weiner CP, Thompson LP 1994. Effect of pregnancy on contraction and endothelium-mediated relaxation of renal and mesenteric arteries. Am. J. Physiol. 267:H41–47
    [Google Scholar]
  55. 55.  Dalle Lucca JJ, Adeagbo ASO, Alsip NL 2000. Influence of oestrous cycle and pregnancy on the reactivity of the rat mesenteric vascular bed. Hum. Reprod. 15:961–68
    [Google Scholar]
  56. 56.  Cooke CL, Davidge ST 2003. Pregnancy-induced alterations of vascular function in mouse mesenteric and uterine arteries. Biol. Reprod. 68:1072–77
    [Google Scholar]
  57. 57.  Meyer MC, Brayden JE, McLaughlin MK 1993. Characteristics of vascular smooth muscle in the maternal resistance circulation during pregnancy in the rat. Am. J. Obstet. Gynecol. 169:1510–16
    [Google Scholar]
  58. 58.  Davidge ST, McLaughlin MK 1992. Endogenous modulation of the blunted adrenergic response in resistance-sized mesenteric arteries from the pregnant rat. Am. J. Obstet. Gynecol. 167:1691–98
    [Google Scholar]
  59. 59.  D'Angelo G, Osol G 1993. Regional variation in resistance artery diameter responses to alpha-adrenergic stimulation during pregnancy. Am. J. Physiol. 264:H78–85
    [Google Scholar]
  60. 60.  Crandall ME, Keve TM, McLaughlin MK 1990. Characterization of norepinephrine sensitivity in the maternal splanchnic circulation during pregnancy. Am. J. Obstet. Gynecol. 162:1296–301
    [Google Scholar]
  61. 61.  Crandall ME, Heesch CM 1990. Baroreflex control of sympathetic outflow in pregnant rats: effects of captopril. Am. J. Physiol. 258:R1417–23
    [Google Scholar]
  62. 62.  Chu ZM, Beilin LJ 1998. Neuropeptide Y and mesenteric sympathetic vasoconstriction in pregnant and non-pregnant Wistar-Kyoto rats. Clin. Exp. Pharmacol. Physiol. 25:630–32
    [Google Scholar]
  63. 63.  Mata KM, Li W, Reslan OM, Siddiqui WT, Opsasnick LA, Khalil RA 2015. Adaptive increases in expression and vasodilator activity of estrogen receptor subtypes in a blood vessel-specific pattern during pregnancy. Am. J. Physiol. Heart Circ. Physiol. 309:H1679–96
    [Google Scholar]
  64. 64.  Marshall SA, Leo CH, Senadheera SN, Girling JE, Tare M, Parry LJ 2016. Relaxin deficiency attenuates pregnancy-induced adaptation of the mesenteric artery to angiotensin II in mice. Am. J. Physiol. Regul. Integr. Comp. Physiol. 310:R847–57
    [Google Scholar]
  65. 65.  Mackey K, Meyer MC, Stirewalt WS, Starcher BC, McLaughlin MK 1992. Composition and mechanics of mesenteric resistance arteries from pregnant rats. Am. J. Physiol. 263:R2–8
    [Google Scholar]
  66. 66.  Conrad KP, Shroff SG 2011. Effects of relaxin on arterial dilation, remodeling, and mechanical properties. Curr. Hypertens. Rep. 13:409–20
    [Google Scholar]
  67. 67.  Smith MC, Murdoch AP, Danielson LA, Conrad KP, Davison JM 2006. Relaxin has a role in establishing a renal response in pregnancy. Fertil. Steril. 86:253–55
    [Google Scholar]
  68. 68.  Ferreira VM, Gomes TS, Reis LA, Ferreira AT, Razvickas CV et al. 2009. Receptor-induced dilatation in the systemic and intrarenal adaptation to pregnancy in rats. PLOS ONE 4:e4845
    [Google Scholar]
  69. 69.  Novak J, Danielson LA, Kerchner LJ, Sherwood OD, Ramirez RJ et al. 2001. Relaxin is essential for renal vasodilation during pregnancy in conscious rats. J. Clin. Investig. 107:1469–75
    [Google Scholar]
  70. 70.  Jeyabalan A, Novak J, Danielson LA, Kerchner LJ, Opett SL, Conrad KP 2003. Essential role for vascular gelatinase activity in relaxin-induced renal vasodilation, hyperfiltration, and reduced myogenic reactivity of small arteries. Circ. Res. 93:1249–57
    [Google Scholar]
  71. 71.  Novak J, Ramirez RJ, Gandley RE, Sherwood OD, Conrad KP 2002. Myogenic reactivity is reduced in small renal arteries isolated from relaxin-treated rats. Am. J. Physiol. Regul. Integr. Comp. Physiol. 283:R349–55
    [Google Scholar]
  72. 72.  Gandley RE, Conrad KP, McLaughlin MK 2001. Endothelin and nitric oxide mediate reduced myogenic reactivity of small renal arteries from pregnant rats. Am. J. Physiol. Regul. Integr. Comp. Physiol. 280:R1–7
    [Google Scholar]
  73. 73.  Murphy JG, Fleming JB, Cockrell KL, Granger JP, Khalil RA 2001. [Ca2+]i signaling in renal arterial smooth muscle cells of pregnant rat is enhanced during inhibition of NOS. Am. J. Physiol. Regul. Integr. Comp. Physiol. 280:R87–99
    [Google Scholar]
  74. 74.  Chu ZM, Beilin LJ 1997. Demonstration of the existence of nitric oxide-independent as well as nitric oxide-dependent vasodilator mechanisms in the in situ renal circulation in near term pregnant rats. Br. J. Pharmacol. 122:307–15
    [Google Scholar]
  75. 75.  Anumba DO, Robson SC, Boys RJ, Ford GA 1999. Nitric oxide activity in the peripheral vasculature during normotensive and preeclamptic pregnancy. Am. J. Physiol. 277:H848–54
    [Google Scholar]
  76. 76.  Amburgey OA, Reeves SA, Bernstein IM, Cipolla MJ 2010. Resistance artery adaptation to pregnancy counteracts the vasoconstricting influence of plasma from normal pregnant women. Reprod. Sci. 17:29–39
    [Google Scholar]
  77. 77.  Schreurs MP, Houston EM, May V, Cipolla MJ 2012. The adaptation of the blood-brain barrier to vascular endothelial growth factor and placental growth factor during pregnancy. FASEB J 26:355–62
    [Google Scholar]
  78. 78.  Cipolla MJ, Vitullo L, McKinnon J 2004. Cerebral artery reactivity changes during pregnancy and the postpartum period: a role in eclampsia?. Am. J. Physiol. Heart Circ. Physiol. 286:H2127–32
    [Google Scholar]
  79. 79.  Euser AG, Cipolla MJ 2005. Resistance artery vasodilation to magnesium sulfate during pregnancy and the postpartum state. Am. J. Physiol. Heart Circ. Physiol. 288:H1521–25
    [Google Scholar]
  80. 80.  Quick AM, Cipolla MJ 2005. Pregnancy-induced up-regulation of aquaporin-4 protein in brain and its role in eclampsia. FASEB J 19:170–75
    [Google Scholar]
  81. 81.  Chapman AC, Cipolla MJ, Chan SL 2013. Effect of pregnancy and nitric oxide on the myogenic vasodilation of posterior cerebral arteries and the lower limit of cerebral blood flow autoregulation. Reprod. Sci. 20:1046–54
    [Google Scholar]
  82. 82.  Chan SL, Cipolla MJ 2011. Relaxin causes selective outward remodeling of brain parenchymal arterioles via activation of peroxisome proliferator-activated receptor-γ. FASEB J 25:3229–39
    [Google Scholar]
  83. 83.  Chan SL, Chapman AC, Sweet JG, Gokina NI, Cipolla MJ 2010. Effect of PPARγ inhibition during pregnancy on posterior cerebral artery function and structure. Front. Physiol. 1:130
    [Google Scholar]
  84. 84.  van der Wijk AE, Schreurs MP, Cipolla MJ 2013. Pregnancy causes diminished myogenic tone and outward hypotrophic remodeling of the cerebral vein of Galen. J. Cereb. Blood Flow Metab. 33:542–49
    [Google Scholar]
  85. 85.  Shynlova O, Kwong R, Lye SJ 2010. Mechanical stretch regulates hypertrophic phenotype of the myometrium during pregnancy. Reproduction 139:247–53
    [Google Scholar]
  86. 86.  Duncan SL. 1969. The partition of uterine blood flow in the pregnant rabbit. J. Physiol. 204:421–33
    [Google Scholar]
  87. 87.  Osol G, Mandalà M 2009. Maternal uterine vascular remodeling during pregnancy. Physiology 24:58–71
    [Google Scholar]
  88. 88.  Palmer SK, Zamudio S, Coffin C, Parker S, Stamm E, Moore LG 1992. Quantitative estimation of human uterine artery blood flow and pelvic blood flow redistribution in pregnancy. Obstet. Gynecol. 80:1000–6
    [Google Scholar]
  89. 89.  Osol G, Barron C, Gokina N, Mandalà M 2009. Inhibition of nitric oxide synthases abrogates pregnancy-induced uterine vascular expansive remodeling. J. Vasc. Res. 46:478–86
    [Google Scholar]
  90. 90.  Ni Y, Meyer M, Osol G 1997. Gestation increases nitric oxide-mediated vasodilation in rat uterine arteries. Am. J. Obstet. Gynecol. 176:856–64
    [Google Scholar]
  91. 91.  Hale SA, Weger L, Mandalà M, Osol G 2011. Reduced NO signaling during pregnancy attenuates outward uterine artery remodeling by altering MMP expression and collagen and elastin deposition. Am. J. Physiol. Heart Circ. Physiol. 301:H1266–75
    [Google Scholar]
  92. 92.  Barron C, Mandalà M, Osol G 2010. Effects of pregnancy, hypertension and nitric oxide inhibition on rat uterine artery myogenic reactivity. J. Vasc. Res. 47:463–71
    [Google Scholar]
  93. 93.  van der Heijden OWH, Essers YPG, Fazzi G, Peeters LLH, De Mey JGR, van Eys GJJM 2005. Uterine artery remodeling and reproductive performance are impaired in endothelial nitric oxide synthase-deficient mice. Biol. Reprod. 72:1161–68
    [Google Scholar]
  94. 94.  van der Heijden OWH, Essers YPG, Spaanderman MEA, De Mey JGR, van Eys GJJM, Peeters LLH 2005. Uterine artery remodeling in pseudopregnancy is comparable to that in early pregnancy. Biol. Reprod. 73:1289–93
    [Google Scholar]
  95. 95.  Fuller R, Colton I, Gokina N, Mandalà M, Osol G 2011. Local versus systemic influences on uterine vascular reactivity during pregnancy in the single-horn gravid rat. Reprod. Sci. 18:723–29
    [Google Scholar]
  96. 96.  Gokina NI, Kuzina OY, Fuller R, Osol G 2009. Local uteroplacental influences are responsible for the induction of uterine artery myogenic tone during rat pregnancy. Reprod. Sci. 16:1072–81
    [Google Scholar]
  97. 97.  Fuller R, Barron C, Mandalà M, Gokina N, Osol G 2009. Predominance of local over systemic factors in uterine arterial remodeling during pregnancy. Reprod. Sci. 16:489–500
    [Google Scholar]
  98. 98.  Mapletoft RJ, Ginther OJ 1975. Adequacy of main uterine vein and the ovarian artery in the local venoarterial pathway for uterine-induced luteolysis in ewes. Am. J. Vet. Res. 36:957–63
    [Google Scholar]
  99. 99.  Celia G, Osol G 2002. Venoarterial communication as a mechanism for localized signaling in the rat uterine circulation. Am. J. Obstet. Gynecol. 187:1653–59
    [Google Scholar]
  100. 100.  Celia G, Osol G 2005. Mechanism of VEGF-induced uterine venous hyperpermeability. J. Vasc. Res. 42:47–54
    [Google Scholar]
  101. 101.  Celia G, Osol G 2005. Uterine venous permeability in the rat is altered in response to pregnancy, vascular endothelial growth factor, and venous constriction. Endothelium 12:81–88
    [Google Scholar]
  102. 102.  Ko NL, John L, Gelinne A, Mandalà M, Osol G 2018. Venoarterial communication mediates arterial wall shear stress-induced maternal uterine vascular remodeling during pregnancy. Am. J. Physiol. Heart Circ. Physiol. 315:H709–17
    [Google Scholar]
  103. 103.  Vita JA, Holbrook M, Palmisano J, Shenouda SM, Chung WB et al. 2008. Flow-induced arterial remodeling relates to endothelial function in the human forearm. Circulation 117:3126–33
    [Google Scholar]
  104. 104.  Bakker EN, Matlung HL, Bonta P, de Vries CJ, van Rooijen N, Vanbavel E 2008. Blood flow-dependent arterial remodelling is facilitated by inflammation but directed by vascular tone. Cardiovasc. Res. 78:341–48
    [Google Scholar]
  105. 105.  Langille BL, O'Donnell F 1986. Reductions in arterial diameter produced by chronic decreases in blood flow are endothelium-dependent. Science 231:405–7
    [Google Scholar]
  106. 106.  Osol G, Moore LG 2014. Maternal uterine vascular remodeling during pregnancy. Microcirculation 21:38–47
    [Google Scholar]
  107. 107.  Hwang M, Berceli SA, Garbey M, Kim NH, Tran-Son-Tay R 2012. The dynamics of vein graft remodeling induced by hemodynamic forces: a mathematical model. Biomech. Model. Mechanobiol. 11:411–23
    [Google Scholar]
  108. 108.  Page KL, Celia G, Leddy G, Taatjes DJ, Osol G 2002. Structural remodeling of rat uterine veins in pregnancy. Am. J. Obstet. Gynecol. 187:1647–52
    [Google Scholar]
  109. 109.  Cipolla M, Osol G 1994. Hypertrophic and hyperplastic effects of pregnancy on the rat uterine arterial wall. Am. J. Obstet. Gynecol. 171:805–11
    [Google Scholar]
  110. 110.  Magness RR, Shideman CR, Habermehl DA, Sullivan JA, Bird IM 2000. Endothelial vasodilator production by uterine and systemic arteries. V. Effects of ovariectomy, the ovarian cycle, and pregnancy on prostacyclin synthase expression. Prostaglandins Lipid Mediat 60:103–18
    [Google Scholar]
  111. 111.  Gokina NI, Goecks T 2006. Upregulation of endothelial cell Ca2+ signaling contributes to pregnancy-enhanced vasodilation of rat uteroplacental arteries. Am. J. Physiol. Heart Circ. Physiol. 290:H2124–35
    [Google Scholar]
  112. 112.  Gokina NI, Kuzina OY, Vance AM 2010. Augmented EDHF signaling in rat uteroplacental vasculature during late pregnancy. Am. J. Physiol. Heart Circ. Physiol. 299:H1642–52
    [Google Scholar]
  113. 113.  Sheibani L, Lechuga TJ, Zhang H, Hameed A, Wing DA et al. 2017. Augmented H2S production via cystathionine-beta-synthase upregulation plays a role in pregnancy-associated uterine vasodilation. Biol. Reprod. 96:664–72
    [Google Scholar]
  114. 114.  Gifford SM, Yi FX, Bird IM 2006. Pregnancy-enhanced Ca2+ responses to ATP in uterine artery endothelial cells is due to greater capacitative Ca2+ entry rather than altered receptor coupling. J. Endocrinol. 190:373–84
    [Google Scholar]
  115. 115.  Boeldt DS, Hankes AC, Alvarez RE, Khurshid N, Balistreri M et al. 2014. Pregnancy programming and preeclampsia: identifying a human endothelial model to study pregnancy-adapted endothelial function and endothelial adaptive failure in preeclamptic subjects. Adv. Exp. Med. Biol. 814:27–47
    [Google Scholar]
  116. 116.  Boeldt DS, Grummer MA, Magness RR, Bird IM 2014. Altered VEGF-stimulated Ca2+ signaling in part underlies pregnancy-adapted eNOS activity in UAEC. J. Endocrinol. 223:1–11
    [Google Scholar]
  117. 117.  Alvarez RE, Boeldt DS, Pattnaik BR, Friedman HL, Bird IM 2017. Pregnancy-adapted uterine artery endothelial cell Ca2+ signaling and its relationship with membrane potential. Physiol. Rep. 5:e13452
    [Google Scholar]
  118. 118.  Senadheera S, Bertrand PP, Grayson TH, Leader L, Murphy TV, Sandow SL 2013. Pregnancy-induced remodelling and enhanced endothelium-derived hyperpolarization-type vasodilator activity in rat uterine radial artery: transient receptor potential vanilloid type 4 channels, caveolae and myoendothelial gap junctions. J. Anat. 223:677–86
    [Google Scholar]
  119. 119.  Ampey BC, Ampey AC, Lopez GE, Bird IM, Magness RR 2017. Cyclic nucleotides differentially regulate Cx43 gap junction function in uterine artery endothelial cells from pregnant ewes. Hypertension 70:401–11
    [Google Scholar]
  120. 120.  Kenny LC, Baker PN, Kendall DA, Randall MD, Dunn WR 2002. Differential mechanisms of endothelium-dependent vasodilator responses in human myometrial small arteries in normal pregnancy and pre-eclampsia. Clin. Sci. 103:67–73
    [Google Scholar]
  121. 121.  Janowiak MA, Magness RR, Habermehl DA, Bird IM 1998. Pregnancy increases ovine uterine artery endothelial cyclooxygenase-1 expression. Endocrinology 139:765–71
    [Google Scholar]
  122. 122.  Habermehl DA, Janowiak MA, Vagnoni KE, Bird IM, Magness RR 2000. Endothelial vasodilator production by uterine and systemic arteries. IV. Cyclooxygenase isoform expression during the ovarian cycle and pregnancy in sheep. Biol. Reprod. 62:781–88
    [Google Scholar]
  123. 123.  Zhang HH, Chen JC, Sheibani L, Lechuga TJ, Chen DB 2017. Pregnancy augments VEGF-stimulated in vitro angiogenesis and vasodilator (NO and H2S) production in human uterine artery endothelial cells. J. Clin. Endocrinol. Metab. 102:2382–93
    [Google Scholar]
  124. 124.  Mandalà M, Gokina N, Osol G 2002. Contribution of nonendothelial nitric oxide to altered rat uterine resistance artery serotonin reactivity during pregnancy. Am. J. Obstet. Gynecol. 187:463–68
    [Google Scholar]
  125. 125.  Nathan L, Cuevas J, Chaudhuri G 1995. The role of nitric oxide in the altered vascular reactivity of pregnancy in the rat. Br. J. Pharmacol. 114:955–60
    [Google Scholar]
  126. 126.  Pastore MB, Talwar S, Conley MR, Magness RR 2016. Identification of differential ER-alpha versus ER-beta mediated activation of eNOS in ovine uterine artery endothelial cells. Biol. Reprod. 94:139
    [Google Scholar]
  127. 127.  Tropea T, De Francesco EM, Rigiracciolo D, Maggiolini M, Wareing M et al. 2015. Pregnancy augments G protein estrogen receptor (GPER) induced vasodilation in rat uterine arteries via the nitric oxide–cGMP signaling pathway. PLOS ONE 10:e0141997
    [Google Scholar]
  128. 128.  Jobe SO, Ramadoss J, Wargin AJ, Magness RR 2013. Estradiol-17β and its cytochrome P450- and catechol-O-methyltransferase-derived metabolites selectively stimulate production of prostacyclin in uterine artery endothelial cells: role of estrogen receptor-α versus estrogen receptor-β. Hypertension 61:509–18
    [Google Scholar]
  129. 129.  Ni Y, May V, Braas K, Osol G 1997. Pregnancy augments uteroplacental vascular endothelial growth factor gene expression and vasodilator effects. Am. J. Physiol. 273:H938–44
    [Google Scholar]
  130. 130.  Osol G, Celia G, Gokina N, Barron C, Chien E et al. 2008. Placental growth factor is a potent vasodilator of rat and human resistance arteries. Am. J. Physiol. Heart Circ. Physiol. 294:H1381–87
    [Google Scholar]
  131. 131.  Storment JM, Meyer M, Osol G 2000. Estrogen augments the vasodilatory effects of vascular endothelial growth factor in the uterine circulation of the rat. Am. J. Obstet. Gynecol. 183:449–53
    [Google Scholar]
  132. 132.  Burger NZ, Kuzina OY, Osol G, Gokina NI 2009. Estrogen replacement enhances EDHF-mediated vasodilation of mesenteric and uterine resistance arteries: role of endothelial cell Ca2+. Am. J. Physiol. Endocrinol. Metab. 296:E503–12
    [Google Scholar]
  133. 133.  Annibale DJ, Rosenfeld CR, Stull JT, Kamm KE 1990. Protein content and myosin light chain phosphorylation in uterine arteries during pregnancy. Am. J. Physiol. 259:C484–89
    [Google Scholar]
  134. 134.  Osol G, Cipolla M 1993. Pregnancy-induced changes in the three-dimensional mechanical properties of pressurized rat uteroplacental (radial) arteries. Am. J. Obstet. Gynecol. 168:268–74
    [Google Scholar]
  135. 135.  Morschauser TJ, Ramadoss J, Koch JM, Yi FX, Lopez GE et al. 2014. Local effects of pregnancy on connexin proteins that mediate Ca2+-associated uterine endothelial NO synthesis. Hypertension 63:589–94
    [Google Scholar]
  136. 136.  Keyes LE, Moore LG, Walchak SJ, Dempsey EC 1996. Pregnancy-stimulated growth of vascular smooth muscle cells: importance of protein kinase C-dependent synergy between estrogen and platelet-derived growth factor. J. Cell Physiol. 166:22–32
    [Google Scholar]
  137. 137.  Vodstrcil LA, Tare M, Novak J, Dragomir N, Ramirez RJ et al. 2012. Relaxin mediates uterine artery compliance during pregnancy and increases uterine blood flow. FASEB J 26:4035–44
    [Google Scholar]
  138. 138.  Eckman DM, Gupta R, Rosenfeld CR, Morgan TM, Charles SM et al. 2012. Pregnancy increases myometrial artery myogenic tone via NOS- or COX-independent mechanisms. Am. J. Physiol. Regul. Integr. Comp. Physiol. 303:R368–75
    [Google Scholar]
  139. 139.  Gokina NI, Mandalà M, Osol G 2003. Induction of localized differences in rat uterine radial artery behavior and structure during gestation. Am. J. Obstet. Gynecol. 189:1489–93
    [Google Scholar]
  140. 140.  Telezhkin V, Goecks T, Bonev AD, Osol G, Gokina NI 2008. Decreased function of voltage-gated potassium channels contributes to augmented myogenic tone of uterine arteries in late pregnancy. Am. J. Physiol. Heart Circ. Physiol. 294:H272–84
    [Google Scholar]
  141. 141.  Veerareddy S, Campbell ME, Williams SJ, Baker PN, Davidge ST 2004. Myogenic reactivity is enhanced in rat radial uterine arteries in a model of maternal undernutrition. Am. J. Obstet. Gynecol. 191:334–39
    [Google Scholar]
  142. 142.  Xiao D, Huang X, Yang S, Zhang L 2009. Direct chronic effect of steroid hormones in attenuating uterine arterial myogenic tone: role of protein kinase C/extracellular signal–regulated kinase 1/2. Hypertension 54:352–58
    [Google Scholar]
  143. 143.  Senadheera S, Bertrand PP, Grayson TH, Leader L, Tare M et al. 2013. Enhanced contractility in pregnancy is associated with augmented TRPC3, L-type, and T-type voltage-dependent calcium channel function in rat uterine radial artery. Am. J. Physiol. Regul. Integr. Comp. Physiol. 305:R917–26
    [Google Scholar]
  144. 144.  D'Angelo G, Osol G 1994. Modulation of uterine resistance artery lumen diameter by calcium and G protein activation during pregnancy. Am. J. Physiol. 267:H952–61
    [Google Scholar]
  145. 145.  Zhu R, Huang X, Hu XQ, Xiao D, Zhang L 2014. Gestational hypoxia increases reactive oxygen species and inhibits steroid hormone-mediated upregulation of Ca2+-activated K+ channel function in uterine arteries. Hypertension 64:415–22
    [Google Scholar]
  146. 146.  Lorca RA, Wakle-Prabagaran M, Freeman WE, Pillai MK, England SK 2018. The large-conductance voltage- and Ca2+ -activated K+ channel and its γ1-subunit modulate mouse uterine artery function during pregnancy. J. Physiol. 596:1019–33
    [Google Scholar]
  147. 147.  Zhu R, Hu XQ, Xiao D, Yang S, Wilson SM et al. 2013. Chronic hypoxia inhibits pregnancy-induced upregulation of SKCa channel expression and function in uterine arteries. Hypertension 62:367–74
    [Google Scholar]
  148. 148.  Murphy TV, Kanagarajah A, Toemoe S, Bertrand PP, Grayson TH et al. 2016. TRPV3 expression and vasodilator function in isolated uterine radial arteries from non-pregnant and pregnant rats. Vasc. Pharmacol. 83:66–77
    [Google Scholar]
  149. 149.  Lu Y, Zhang H, Gokina N, Mandalà M, Sato O et al. 2008. Uterine artery myosin phosphatase isoform switching and increased sensitivity to SNP in a rat L-NAME model of hypertension of pregnancy. Am. J. Physiol. Cell Physiol. 294:C564–71
    [Google Scholar]
  150. 150.  Lechuga TJ, Zhang HH, Sheibani L, Karim M, Jia J et al. 2015. Estrogen replacement therapy in ovariectomized nonpregnant ewes stimulates uterine artery hydrogen sulfide biosynthesis by selectively up-regulating cystathionine β-synthase expression. Endocrinology 156:2288–98
    [Google Scholar]
/content/journals/10.1146/annurev-physiol-020518-114435
Loading
/content/journals/10.1146/annurev-physiol-020518-114435
Loading

Data & Media loading...

  • Article Type: Review Article
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error