The Vascular Actions of Relaxin

  • Arundhathi Jeyabalan
  • Sanjeev G. Shroff
  • Jaqueline Novak
  • Kirk P. Conrad
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 612)


Relaxin is emerging as a hormone with important vascular actions. Much of our recently gained knowledge of relaxin in this context has stemmed from investigations of maternal vascular adaptations to pregnancy in which the hormone is turning out to be an important mediator. This chapter is separated into three parts. In Part 1, we discuss relaxin in the setting of normal vascular function and focus on systemic hemodynamics and arterial mechanical properties, renal and other peripheral circulations, angiogenesis, as well as the cellular mechanisms of the vasodilatory actions of relaxin. In this section, we also summarize the evidence for an arterial-derived relaxin ligand-receptor system. In Part 2, we present relaxin in the context of vascular dysfunction and the implications for relaxin as a therapeutic agent in renal and cardiac diseases, ischemia and reperfusion injury, pulmonary hypertension, vascular inflammation and preeclampsia. Finally, in Part 3, we highlight some of the controversies and unresolved issues, as well as suggest a general direction for future relaxin research that is urgendy needed.


Renal Vasodilation Renal Circulation Relaxin Receptor Myogenic Reactivity Cardiac Anaphylaxis 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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  1. 1.
    Dallenbach-Hellweg G, Dawson AB, Hisaw FL. The effect of relaxin on the endometrium of monkeys-histological and histochemical studies. Am J Anatomy 1966;119:61–78.Google Scholar
  2. 2.
    Hisaw FL, Hisaw FL, Jr, Dawson AB. Effects of relaxin on the endothelium of endometrial blood vessels in monkeys (Macaca mulatta). Endocrinology 1967;81:375–385.PubMedGoogle Scholar
  3. 3.
    Shroff SG. Pulsatile arterial load and cardiovasculat function: fact, fiction and wishful thinking. Therapeutic Research 1998;19:59–66.Google Scholar
  4. 4.
    Poppas A, Shroff SG, Korcarz CE et al. Serial assessment of the cardiovascular system in normal pregnancy. Role of arterial compliance and pulsatile arterial load. Circulation 1997;95:2407–2415.PubMedGoogle Scholar
  5. 5.
    Novak J, Danielson LA, Kerchner LJ et al. Relaxin is essential for renal vasodilation during pregnancy in conscious rats. J Clin Invest 2001;107:1469–1475.PubMedGoogle Scholar
  6. 6.
    Conrad KP, Debrah DO, Novak J et al. Relaxin modulates systemic arterial resistance and compliance in conscious, nonpregnant rats. Endocrinology 2004;145:3289–3296.PubMedGoogle Scholar
  7. 7.
    Shroff S, Berger D, Lang R et al. Physiologic relevance of T-Tube model parameters with emphasis on arterial compliances. Am J Physiol (Heart Circ Physiol 38) 1995;269:H365–H374.Google Scholar
  8. 8.
    Debrah DO, Conrad KP, Danielson LA et al. Effects of relaxin on systemic arterial hemodynamics and mechanical properties in conscious rats: gender dependency and dose response. J Appl Physiol 2005;98:1013–1020.PubMedGoogle Scholar
  9. 9.
    Debrah DO, Conrad KP, Jeyabalan A et al. Relaxin increases cardiac output and reduces systemic arterial load in hypertensive rats. Hypertension 2005;46:745–750.PubMedGoogle Scholar
  10. 10.
    Debrah DO, Novak J, Matthews JE et al. Relaxin is essential for systemic vasodilation and increased global arterial compliance during early pregnancy in conscious rats. Endocrinol 2006;147:5126–31.Google Scholar
  11. 11.
    Gandley RE, Conrad KP and McLaughlin MK. Endothelin and nitric oxide mediate reduced myogenic reactivity of small renal arteries from pregnant rats. Am J Physiol Regul Integr Comp Physiol 2001;280:R1–7.PubMedGoogle Scholar
  12. 12.
    Gandley RE, Griggs KC, Conrad KP et al. Intrinsic tone and passive mechanics of isolated renal arteries from virgin and late pregnant rats. Am J Physiol 1997;273:R22–R27.PubMedGoogle Scholar
  13. 13.
    McLaughlin MK, Keve TM. Pregnancy-induced changes in resistance blood vessels. Am J Obstet Gynecol 1986;155:1296–1299.PubMedGoogle Scholar
  14. 14.
    Conrad KP, Lindheimer MD Renal and cardiovascular alterations. In: Lindheimer MD, Cunningham FG, Roberts JM eds. Appleton and Lange, Chesley’s Hypertensive Disorders in Pregnancy: Second Edition. Chapter 8. Stamford, CT, 1999;263–326.Google Scholar
  15. 15.
    Conrad KP Mechanisms of renal vasodilation and hyperfiltration during pregnancy. J Soc Gynecol Invest 2004;11, 438–48.Google Scholar
  16. 16.
    Conrad KP, Novak J Emerging role of relaxin in renal and cardiovascular function. Am J Physiol Regul Integr Comp Physiol 2004;287:4250–R261.Google Scholar
  17. 17.
    Davison JM, Noble MC. Serial changes in 24 hour creatinine clearance during normal menstrual cycles and the first trimester of pregnancy. Br J Obstet Gynaecol 1981;88:10–7.PubMedGoogle Scholar
  18. 18.
    Baylis C The mechanism of the increase in glomerular filtration rate in the twelve-day pregnant rat. J Physiol 1982;22:1982;136–45.Google Scholar
  19. 19.
    Roberts M, Lindheimer MD, Davison JM. Altered glomerular permselectivity to neutral dextrans and heteroporous membrane modeling in human pregnancy. Am J Physiol 1996;270:F338–43.PubMedGoogle Scholar
  20. 20.
    Conrad KP. Renal hemodynamics during pregnancy in chronically catheterized, conscious rats. Kidney Int 1984;26:24–9.PubMedGoogle Scholar
  21. 21.
    Sherwood OD Relaxin. In: The Physiology of Reproduction. Eds: Knobil E, Neill JD, Greenwald GS, Markert CL, Pfaff DW, Raven, NY 1994;861–1009.Google Scholar
  22. 22.
    Danielson LA, Sherwood OD, Conrad KP. Relaxin is a potent renal vasodilator in conscious rats. J Clin Invest 1999;103:525–33.PubMedGoogle Scholar
  23. 23.
    Danielson LA, Kerchner 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:R1298–304.PubMedGoogle Scholar
  24. 24.
    Conrad KP, Colpoys MC. Evidence against the hypothesis that prostaglandins are the vasodepressor agents of pregnancy. Serial studies in chronically instrumented conscious rats. J Clin Invest 1986;77:236–45.PubMedGoogle Scholar
  25. 25.
    Danielson LA, Conrad KP. Acute blockade of nitric oxide synthase inhibits renal vasodilation and hyperfiltration during pregnancy in chronically instrumented, conscious rats. J Clin Invest 1995;96:482–90.PubMedGoogle Scholar
  26. 26.
    Novak J, Reckelhoff J, Bumgarner L et al. Reduced sensitivity of the renal circulation to angiotensin II in pregnant rats. Hypertension 1997;30:580–4.PubMedGoogle Scholar
  27. 27.
    Novak J, Ramirez RJ, Gandley RE et al. Myogenic reactivity is reduced in small renal arteries isolated from relaxin-treated rats. Am J Physiol Regul Integr Comp Physiol 2002;283:R349–55.PubMedGoogle Scholar
  28. 28.
    Danielson LA, Conrad KP. Time course and dose response of relaxin-mediated renal vasodilation, hyperfiltration and changes in plasma osmolality in conscious rats. J App Physiol 2003;95:1509–1514.Google Scholar
  29. 29.
    Smith MC, Danielson LA, Conrad KP et al. Influence of recombinant human relaxin on renal haemodynamics in humans. J Am Soc Nephrol 2006;17:3192–7.PubMedGoogle Scholar
  30. 30.
    Erikson MS, Unemori EN. Relaxin clinical trials in systemic sclerosis In: Tregear GW, Ivell R, Bathgate RA et al. eds. Relaxin 2000. Kluwer Academic Publishers, MA 2000;373–381.Google Scholar
  31. 31.
    Smith MC, Murdoch AP, Danielson LA et al. Relaxin has a role in establishing a renal response in pregnancy. Fertil Steril 2006;86:253–255.PubMedGoogle Scholar
  32. 32.
    Novak J, Rajakumar A, Miles TM et al. Nitric oxide synthase isoforms in the rat kidney during pregnancy. J Soc Gynecol Invest 2004;11:280–288.Google Scholar
  33. 33.
    Alexander BT, Miller MT, Kassab L et al. Differential Expression of Renal Nitric Oxide Synthase Isoforms During Pregnancy in Rats. Hypertension Journal of the American Heart Association 1999;33:435–439.Google Scholar
  34. 34.
    Kerchner LJ, Novak J, Hanley-Yanez K et al. Evidence against the hypothesis that endothelial endothelin B receptor expression is regulated by relaxin and pregnancy. Endocrinol 2005;146:2791–7.Google Scholar
  35. 35.
    Dschietzig T, Bartsch C, Richter C et al. Relaxin, a pregnancy hormone, is a functional endothelin-1 antagonist. Circ Res 2003;92:32–40.PubMedGoogle Scholar
  36. 36.
    Jeyabalan A, Novak J, Danielson LA et al. Essential role for vascular gelatinase activity in relaxin-induced renal vasodilation, hyperflltration and reduced myogenic reactivity of small arteries. Circ Res 2003;93:1249–1257.PubMedGoogle Scholar
  37. 37.
    Novak J, Conrad KP. Small renal arteries isolated from ETB receptor deficient rats fail to exhibit the normal maternal adaptation to pregnancy. FASEB J 2004;18(5) Part I, abstract #205.32.Google Scholar
  38. 38.
    Jeyabalan A, Kerchner LJ, Fisher MC et al. Matrix metalloproteinase-2 activity, protein, mRNA and tissue inhibitors in small arteries from pregnant and relaxin-treated nonpregnant rats. J Applied Physiol 2006;100:1955–1963.Google Scholar
  39. 39.
    Jeyabalan A, Novak J, Doty KD et al. Vascular matrix metalloproteinase-9 mediates the inhibition of myogenic reactivity in small arteries isolated from rats after short term administration of relaxin. Endocrinology 2007;189:197.Google Scholar
  40. 40.
    Matthews JE, Rubin JP, Novak J et al. Vascular Endothelial Growth Factor (VEGF) Is a New Player In Slow Relaxin (Rix) Vasodilatory Pathway. Reproductive SCI 2007;14(1 suppl):114A.Google Scholar
  41. 41.
    Fisher C, MacLean M, Morecroft I et al. Is the pregnancy hormone relaxin also a vasodilator peptide secreted by the heart? Circulation 2002;106:292–295.PubMedGoogle Scholar
  42. 42.
    Matthews JE, Rubin JP, Novak J et al. Relaxin (Rix) Induces Fast Relaxation In some Rat and Human Arteries Mediated By P13 Kinase And Nitric Oxide. Reproductive SCI 2007;14(1 suppl):114A.Google Scholar
  43. 43.
    Bani D, Failli P, Bello MG et al. Relaxin activates the L-arginine-nitric oxide pathway in vascular smooth muscle cells in culture. Hypertension 1998;31:1240–1247.PubMedGoogle Scholar
  44. 44.
    Failli P, Nistri S, Quattrone S et al. Relaxin up-regulates inducible nitric oxide synthase expression and nitric oxide generation in rat coronary endothelial cells. FASEB Journal 2002;16:252–254.PubMedGoogle Scholar
  45. 45.
    Quattrone S, Chiappini L, Scapagnini G et al. Relaxin potentiates the expression of inducible nitric oxide synthase by endothelial cells from human umbilical vien in in vitro culture. Molecular Hum Reprod 2004; Vol.10, No. 5:325–330.Google Scholar
  46. 46.
    Sladek SM, Magness RR, Conrad KP. Nitric oxide and pregnancy. Am J Physiol 1997;272:R441–463.PubMedGoogle Scholar
  47. 47.
    Conrad KP, Gandley RE, Ogawa T et al. Endothelin mediates renal vasodilation and hyperflltration during pregnancy in chronically instrumented conscious rats. Am J Physiol Renal Physiol 1999;276:F767–776.Google Scholar
  48. 48.
    Bani ST, Bigazzi M, Bani D et al. Relaxin-induced increased coronary flow through stimulation of nitric oxide production. Br J Pharmacol 1995;116:1589–1594.PubMedGoogle Scholar
  49. 49.
    Vasilenko P, Mead JP, Weidmann JE et al. Uterine growth-promoting effects of relaxin: a morphometric and histological analysis. Biol Reprod 1986;35:987–995.PubMedGoogle Scholar
  50. 50.
    Kohsaka T, Min G, Lukas G et al. Identification of specific relaxin-binding cells in the human female. Biol Reprod 1998;59:991–999.PubMedGoogle Scholar
  51. 51.
    Min G, Sherwood OD. Identification of specific relaxin-binding sites in the cervix, mammary glands, nipples, small intestine and skin of pregnant pigs. Biol Reprod 1996;55:1243–1252.PubMedGoogle Scholar
  52. 52.
    Novak J. Relaxin increases uterine blood flow in conscious nonpregnant rats and decreases myogenic reactivity in isolated uterine arteries. FASEB J 2002;16:A824.Google Scholar
  53. 53.
    Schramm W, Einer-Jensen N, Brown MB et al. Effect of four primary prostaglandins and relaxin on blood flow in the ovine endometrium and myometrium. Biol Reprod 1984;30:523–531.PubMedGoogle Scholar
  54. 54.
    Roche PJ, Crawford RJ, Tregear GW. A single-copy relaxin-like gene sequence is present in sheep. Mol Cell Endocrinol 1993;91:21–28.PubMedGoogle Scholar
  55. 55.
    Unemori EN, Erikson ME, Rocco SE et al. Relaxin stimulates expression of vascular endothelial growth factor in normal human endometrial cells in vitro and is associated with menometrorrhagia in women. Hum Reprod 1999;14:800–806.PubMedGoogle Scholar
  56. 56.
    Jauniaux E, Johnson MR, Jurkovic D et al. The role of relaxin in the development of the uteroplacental circulation in early pregnancy. Obstet Gynecol 1994;84:338–342.PubMedGoogle Scholar
  57. 57.
    Petersen LK, Svane D, Uldbjerg N et al. Effects of human relaxin on isolated rat and human myometrium and uteroplacental arteries. Obstet Gynecol 1991;78:757–762.PubMedGoogle Scholar
  58. 58.
    Dombrowski MP, Savoy-Moore RT, Swartz K et al. Effect of porcine relaxin on the human umbilical artery. J Reprod Med 1986;31:467–472.PubMedGoogle Scholar
  59. 59.
    Bani G, Bani TS, Bigazzi M et al. Effects of relaxin on the micorvasculature of mouse mammary gland. Histol Histopath 1988;3:337–343.Google Scholar
  60. 60.
    Bigazzi M, Bani G, Bani ST et al. Relaxin: a mammotropic hormone promoting growth and differentiation of the pigeon crop sac mucosa. Acta Endocrinologica 1988;117:181–188.PubMedGoogle Scholar
  61. 61.
    Bani D, Nistri S, Quattrone S et al. The vasorelaxant hormone relaxin induces changes in liver sinusoid microcirculation: a morphologic study in the rat. J Endocrinol 2001;171:541–549.PubMedGoogle Scholar
  62. 62.
    Massicotte G, Parent A, St-Louis J. Blunted responses to vasoconstrictors in mesenteric vasculature but not in portal vein of spontaneously hypertensive rats treated with relaxin. Proc Soc Exp Biol Med 1989;190:254–259.PubMedGoogle Scholar
  63. 63.
    Bigazzi M, Del Mese A, Petrucci F et al. The local administration of relaxin induces changes in the microcirculation of the rat mesocaecum. Acta Endocrinologica 1986;112:296–299.PubMedGoogle Scholar
  64. 64.
    Goldsmith LT, Weiss G, Palejwala S et al. Relaxin regulation of endometrial structure and function in the rhesus monkey. PNAS 2004; 101(13).Google Scholar
  65. 65.
    Palejwala S, Tseng L, Wojtczuk A et al. Relaxin Gene and Protein Expression and its Regulation of Procollagenase and Vascular Endothelial Growth Factor in Human Endometrial Cells. Biol Reprod 2002; 66:1743–1748.PubMedGoogle Scholar
  66. 66.
    Shirota K, Tateishi K, Emotok et al. Relaxin-induced angiogenesis in ovary contributes to follicle development. Ann NY Acad Sci. 2005;1041:144–6.PubMedGoogle Scholar
  67. 67.
    Silvertown JD, Ng J, Sato T et al. H2 relaxin overexpression increases in vivo prostate xenograft tumor growth and angiogenesis. Int J Cancer 2006;118:62–73.PubMedGoogle Scholar
  68. 68.
    Unemori EN, Lewis M, Constant J et al. Relaxin induces vascular endothelial growth factor expression and angiogenesis selectively at wound sites. Wound Repair Regen 2000;8:361–370.PubMedGoogle Scholar
  69. 69.
    Norrby K, Bani D, Bigazzi M et al. Relaxin, a potent microcirculatory effector, is not angiogenic. Int J Microcirc 1996;16:227–231.Google Scholar
  70. 70.
    Huang X, Arnold G, Lewis M et al. Effect of relaxin on normal and impaired wound healing in rodents.In: Tregear GW, Ivell, R., Bathgate, RA, Wade, JD Dordrecht, eds. Relaxin 2000: Proceedings of the third international conference on relaxin and related peptides, The Netherlands: Kluwer Academic Publishers 2001;393–397.Google Scholar
  71. 71.
    Lewis M, Deshpande U, Guzman L et al. Systemic relaxin administration stimulates angiogenic cytokine expression and vessel formation in a rat myocardial infarct model. In: Tregear GW, Ivell, R, Bathgate, RA, Wade, JD Dordrecht, eds. Relaxin 2000: Proceedings of the third international conference on relaxin and related peptides, The Netherlands: Kluwer Academic Publishers, 2001;159–167.Google Scholar
  72. 72.
    Novak J, Parry LJ, Matthews JE et al. Evidence for local relaxin ligand-receptor expression and function in arteries. FASEB J 20, 2006;2352–2362.PubMedGoogle Scholar
  73. 73.
    Dschietzig T, Richter C, Bartsch C et al. The pregnancy hormone relaxin is a player in human heart failure. FASEB Journal 2001;15:2187–2195.PubMedGoogle Scholar
  74. 74.
    Palejwala S, Stein DE, Weiss G et al. Relaxin positively regulates matrix metalloproteinase expression in human lower uterine segment fibroblasts using a tyrosine kinase signaling pathway. Endocrinology 2001;142:3405–3413.PubMedGoogle Scholar
  75. 75.
    Unemori EN, Amento EP. Relaxin modulates synthesis and secretion of procollagenase and collagen by human dermal fibroblasts. J Biol Chem 1990;265:10681–10685.PubMedGoogle Scholar
  76. 76.
    Unemori EN, Pickford LB, Salles AL et al. Relaxin induces an extracellular matrix-degrading phenotype in human lung fibroblasts in vitro and inhibits lung fibrosis in a murine model in vivo. J Clin Invest 1996;98:2739–2745.PubMedGoogle Scholar
  77. 77.
    Samuel CS, Zhao C, Bond CP et al. Relaxin-1-deficient mice develop an age-related progression of renal fibrosis. Kidney Int 2004;65:2054–2064.PubMedGoogle Scholar
  78. 78.
    Garber SL, Mirochnik Y, Brecklin CS et al. Relaxin decreases renal interstitial fibrosis and slows progression of renal disease. Kidney Int 2001;59:876–882.PubMedGoogle Scholar
  79. 79.
    Garber SL, Mirochnik Y, Brecklin C et al. Effect of relaxin in two models of renal mass reduction. Am J Nephrol 2003;23:8–12.PubMedGoogle Scholar
  80. 80.
    Huang X, Cheng Z, Sunga J et al. Systemic administration of recombinant human relaxin (RHRLX) ameliorates the acute cyclosporine nephrotoxicity in rats. J Heart Lung Transplant 2001;20:253.PubMedGoogle Scholar
  81. 81.
    McDonald GA, Sarkar P, Rennke H et al. Relaxin increases ubiquitin-dependent degradation of fibronectin in vitro and ameliorates renal fibrosis in vivo. Am J Physiol Renal Physiol 2003;285(1):F59–67.PubMedGoogle Scholar
  82. 82.
    Samuel CS, Hewitson TD. Relaxin in cardiovascular and renal disease. Kidney Int 2006;69(9):1498–502.PubMedGoogle Scholar
  83. 83.
    Danielson LA, Welford A, Harris A. Relaxin Improves Renal Function and Histology in Aging Munich Wistar Rats. J Am Soc Nephrol 2006;17(5):1325–33.PubMedGoogle Scholar
  84. 84.
    Taylor MJ, Clark, CL. Evidence for a novel source of relaxin: atrial cardiocytes. J Endocrinol 1994;143:R5–R8.PubMedGoogle Scholar
  85. 85.
    Masini E, Bani D, Bello MG et al. Relaxin counteracts myocardial damage induced by ischemia-reperfusion in isolated guinea pig hearts: evidence for an involvement of nitric oxide. Endocrinology 1997;138:4713–4720.PubMedGoogle Scholar
  86. 86.
    Bani D, Masini E, Bello MG et al. Relaxin protects against myocardial injury caused by ischemia and reperfusion in rat heart. Am J Pathol 1998;152:1367–1376.PubMedGoogle Scholar
  87. 87.
    Masini E, Nistri S, Vannacci A et al. Relaxin inhibits the activation of human neutrophils: involvement of the nitric oxide pathway. Endocrinology 2004;145(3):1106–12.PubMedGoogle Scholar
  88. 88.
    Nistri S, Chiappini L, Sassoli C et al. Relaxin inhibits lipopolysaccharide-induced adhesion of neutrophils to coronary endothelial cells by a nitric oxide-mediated mechanism. FASEB Journal 2003;17(14):2109–11.PubMedGoogle Scholar
  89. 89.
    Bani D, Ballati L, Masini E et al. Relaxin counteracts asthma-like reaction induced by inhaled antigen in sensitized guinea pigs. Endocrinology 1997;138:1909–1915.PubMedGoogle Scholar
  90. 90.
    Masini E, Bani D, Bigazzi M et al. Effects of relaxin on mast cells: In vitro and in vivo studies in rats and guinea pigs. J Clin Invest 1994;94:1974–1980.PubMedGoogle Scholar
  91. 91.
    Bani D, Bigazzi M, Masini E et al. Relaxin depresses platelet aggregation: in vitro studies on isolated human and rabbit platelets. Lab Invest 1995;73:709–716.PubMedGoogle Scholar
  92. 92.
    Zhang J, Qi YF, Geng B et al. Effect of relaxin on myocardial ischemia injury induced by isoproterenol. Peptides 2005;26(9):1632–9.PubMedGoogle Scholar
  93. 93.
    Perna AM, Masini E, Nistri S. Human recombinant relaxin reduces heart injury and improves ventricular performance in a swine model of acute myocardial infarction. Ann N Y Acad Sci 2005;1041:431–3.PubMedGoogle Scholar
  94. 94.
    Bani D, Nistri S, Sacchi TB et al. Basic progress and future therapeutic perspectives of relaxin in ischemic heart disease. Ann N Y Acad Sci 2005;1041:423–30.PubMedGoogle Scholar
  95. 95.
    Du X-J, Samuel CS, Gao X-M et al. Increased myocardial collagen and ventricular diastolic dysfunction in relaxin deficient mice: a gender-specific phenotype. Cardiovasc Res 2003;57:395–404.PubMedGoogle Scholar
  96. 96.
    Samuel CS, Unemori EN, Mookerjee I et al. Relaxin modulates cardiac fibroblast proliferation, differentiation and collagen production and reverses cardiac fibrosis in vivo. Endocrinology 2004;145(9):4125–33.PubMedGoogle Scholar
  97. 97.
    Kompa AR, Samuel CS, Summers RJ. Inotropic responses to human gene 2 (B29) relaxin in a rat model of myocardial infarction (MI): effect of pertussis toxin. Br J Pharmacol 2002;137:710–718.PubMedGoogle Scholar
  98. 98.
    Osheroff PL, King KL. Binding and cross-linking of 32P-labeled human relaxin to human uterine cells and primary rat atrial cardiomyocytes. Endocrinology 1995;136:4377–4381.PubMedGoogle Scholar
  99. 99.
    Lekgabe ED, Kiriazis H, Zhao C et al. Relaxin reverses cardiac and renal fibrosis in spontaneously hypertensive rats. Hypertension 2005;46(2):412–8.PubMedGoogle Scholar
  100. 100.
    Dschietzig T, Bartsch C, Kinkel T et al. Myocardial relaxin counteracts hypertrophy in hypertensive rats. Ann N Y Acad Sci 2005;1041:441–3.PubMedGoogle Scholar
  101. 101.
    Krüger S, Graf J, Merx MW et al. Relaxin kinetics during dynamic exercise in patients with chronic heart failure. Eur J Intern Med 2004;15:4–56.Google Scholar
  102. 102.
    Hassink RJ, Brutel de la Riviere A, Mummery CL et al. Transplantation of cells for cardiac repair. J Am Coll Cardiol 2003;41(5):711–7.PubMedGoogle Scholar
  103. 103.
    Dowell JD, Rubart M, Pasumarthi KB et al. Myocyte and myogenic stem cell transplantation in the heart. Cardiovasc Res 2003;58(2):336–50.PubMedGoogle Scholar
  104. 104.
    Murry CE, Wiseman RW, Schwartz SM et al. Myoblast transplantation for repair of myocardial necrosis. J Clin Invest 1996;98(11):2512–23.PubMedGoogle Scholar
  105. 105.
    Taylor DA, Atkins BZ, Hungspreugs P et al. Regenerating functional myocardium: improved performance after skeletal myoblast transplantation. [erratum appears in Nat Med 1998; 4(10):1200]. Nat Med 1998;4(8):929–33.PubMedGoogle Scholar
  106. 106.
    Formigli L, Francini F, Chiappini L et al. Relaxin favors the morphofunctional integration between skeletal myoblasts and adult cardiomyocytes in coculture. Ann N Y Acad Sci 2005;1041:444–5.PubMedGoogle Scholar
  107. 107.
    Masini E, Zagli G, Ndisang JF et al. Protective effect of relaxin in cardiac anaphylaxis: involvement of the nitric oxide pathway. Brit J Pharmacol 2002;137:337–344.Google Scholar
  108. 108.
    Wilson BC, Milne P, Saleh TM. Relaxin pretreatment decreases infarct size in male rats after middle cerebral artery occlusion. Ann N Y Acad Sci 2005;1041:223–8.PubMedGoogle Scholar
  109. 109.
    Nistri S, Bani D. Relaxin in vascular physiology and pathophysiology: possible implications in ischemic brain disease. Curr Neurovasc Res 2005;2(3):225–3.PubMedGoogle Scholar
  110. 110.
    Wilson BC, Connell B, Saleh TM. Relaxin-induced reduction of infarct size in male rats receiving MCAO is dependent on nitric oxide synthesis and not estrogenic mechanisms. Neurosci Lett 2006;393(2–3):160–4.PubMedGoogle Scholar
  111. 111.
    Masini E, Cuzzocrea S, Mazzon E et al. Protective effects of relaxin in ischemia/reperfusion-induced intestinal injury due to splanchnic artery occlusion. Br J Pharmacol 2006;148:1124–32.PubMedGoogle Scholar
  112. 112.
    Boehnert MU, Hilbig H, Armbruster FP. Relaxin as an additional protective substance in preserving and reperfusion solution for liver transplantation, shown in a model of isolated perfused rat liver. Ann N Y Acad Sci 2005;1041:434–40.PubMedGoogle Scholar
  113. 113.
    Tozzi CA, Poiani GJ, McHugh NA et al. Recombinant human relaxin reduces hypoxic pulmonary hypertension in the rat. Pulm Pharmacol Ther 2005;18(5):346–53.PubMedGoogle Scholar
  114. 114.
    Figueiredo KA, Mui AL, Nelson CC et al. Relaxin stimulates leukocyte adhesion and migration through a relaxin receptor LGR7-dependent mechanism. J Biol Chem 2006;281(6):3030–9.PubMedGoogle Scholar
  115. 115.
    Szlachter BN, Quagliarello J, Jewelewicz R et al. Relaxin in normal and pathogenic pregnancies. Obstet Gynecol 1982;59(2):167–70.PubMedGoogle Scholar
  116. 116.
    Rajakumar A, Brandon HM, Daftary A et al. Evidence for the functional activity of hypoxia-inducible transcription factors overexpressed in preeclamptic placentae. Placenta 2004;25(10):763–9.PubMedGoogle Scholar
  117. 117.
    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 preeclampsia. J Clin Invest. 2003;111(5):600–2.Google Scholar
  118. 118.
    Venkatesha S, Toporsian M, Lam C et al. Soluble endoglin contributes to the pathogenesis of preeclampsia. Nat Med. 2006;12(6);642–9.PubMedGoogle Scholar
  119. 119.
    Li Y, Brookes Z, Kaufman S. Acute and chronic effects of relaxin on vasoactivity, myogenic reactivity and compliance of the rat mesenteric arterial and venous vasculature. Regul Pept 2005;132 41–46.PubMedGoogle Scholar

Copyright information

© Landes Bioscience and Springer Science+Business Media 2007

Authors and Affiliations

  • Arundhathi Jeyabalan
    • 1
  • Sanjeev G. Shroff
    • 2
  • Jaqueline Novak
    • 3
  • Kirk P. Conrad
    • 4
  1. 1.Department of Obstetrics, Gynecology and Reproductive SciencesUniversity of Pittsburgh School of Medicine Magee-Womens Research InstitutePittsburghUSA
  2. 2.Department of BioengineeringUniversity of Pittsburgh PittsburghPennsylvaniaUSA
  3. 3.Department of BiologyWalsh UniversityCantonUSA
  4. 4.Department of Physiology and Functional GenomicsUniversity of Florida College of MedicineGainesvilleUSA

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