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Developmental Regulatlon of the Cardiac Renin-Angiotensin System: Expression and Associatlon With Growth and Apoptosis

  • David E. Dostal
  • Rachel A. Hunt
  • Chris E. Kule
  • Kenneth M. Baker
Part of the Progress in Experimental Cardiology book series (PREC, volume 2)

Summary

Identification and elucidation of the roles of humoral factors involved in cardiogenesis and other aspects of cardiac growth will be important for the overall understanding of how the heart develops and functions. Angiotensin (Ang) II has been demonstrated to have important in vivo and in vitro growth-related effects in the neonate and adult myocardium. However, very little is known regarding the regulation of the cardiac renin-angiotensin system (RAS) and the role of Ang II receptors at any developmental stage. Enhanced expression of RAS during fetal and neonatal development suggests that locally produced Ang II exerts autocrine and paracrine influences on cardiogenesis and cardiac growth in these stages of development. Utilization of transgenic models and specific nonpeptide Ang II receptor antagonists will be useful in determining the roles of AT1 and AT2 receptors, respectively, in the regulation of the cardiac RAS, myocardial growth, and apoptosis in the developing rat heart. These studies may provide a better understanding of the effects of Ang II receptors on cellular and molecular aspects of cardiac development and thus lead to improved therapeutic interventions for cardiovascular disease.

Keywords

Cardiac Hypertrophy Cardiac Fibroblast Cardiac Growth Angiotensin Blockade Human Cardiac Fibroblast 
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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References

  1. 1.
    Antin PB, Yatskievych T, Domtnguez JL, Chieffi P. 1969. Regulation of avian precardiac mesoderm development by insulin and insulin-like growth factors, J Cellular Physiol 168:42–50.CrossRefGoogle Scholar
  2. 2.
    Sheng Z, Pennica D, Wood WI, Chien KR. 1996. Cardiotrophin-1 displays early expression in the murine heart tube and promotes cardiac myocyte survival. Development 122:419–428.PubMedGoogle Scholar
  3. 3.
    Mima T, Ueno H, Fischman DA, Williams LT, Mikawa T. 1995. Fibroblast growth factor receptor is required for in vivo cardiac myocyte proliferation at early embryonic stages of heart development. Proc Natl Acad Sci USA 92:467–471.PubMedCrossRefGoogle Scholar
  4. 4.
    Dostal DE, Baker KM. 1992. Angiotensin II stimulation of left ventricular hypertrophy in adult rat heart: mediation by the AT1 receptor. Am J Hypertens 5:276–280.PubMedGoogle Scholar
  5. 5.
    Schorb W, Booz GW, Dostal DE, Conrad KM, Chang KC, Baker KM. 1993. Angiotensin II is mitogenic in neonatal rat cardiac fibroblasts, Circ Res 72:1245–1254.PubMedCrossRefGoogle Scholar
  6. 6.
    Booz GW, Baker KM. 1996. Role of type 1 and type 2 angiotensin receptors in angiotensin II-induced cardiomyocyte hypertrophy. Hypertension 28:635–640.PubMedCrossRefGoogle Scholar
  7. 7.
    Xavier-Vidal R, Mandarim-de-Lacerda CA. 1995. Cardiomyocyte proliferation and hypertrophy in the human fetus: Quantitative study of the myocyte nuclei. Bull Assoc Anat 79:27–31.Google Scholar
  8. 8.
    Sugi Y, Lough J. 1995. Activin-A and FGF-2 mimic the inductive effects of anterior endoderm on terminal cardiac myogenesis in vitro. Development Biol 168:567–574.CrossRefGoogle Scholar
  9. 9.
    Lyons GE, Schiaffino S, Sassoon D, Barton P, Buckingham M. 1990. Developmental regulation of myosin gene expression in mouse cardiac muscle. J Cell Biol 111:2427–2436.PubMedCrossRefGoogle Scholar
  10. 10.
    Ferrans VJ, Rodriguez ER. 1987. Evidence of myocyte hyperplasia in hypertrophic cardiomyopathy and other disorders with myocardial hypertrophy. Zeitschrift fur Kardiologie 76(Suppl 3):20–25.PubMedGoogle Scholar
  11. 11.
    Kaufman MH. 1992. The atlas of mouse development. New York: Academic Press.Google Scholar
  12. 12.
    Beaudoin AR. 1980. Embryology and teratology. In The laboratory rat. Vol. II. Ed. HJ Baker, JR Lindsey, and SH Weisbroth, 75–101. New York: Academic Press.Google Scholar
  13. 13.
    LF, Wang X, Capasso JM, Gerdes AM. 1996. Rapid transition of cardiac myocytes from hyperplasia to hypertrophy during postnatal development. J Mol Cell Cardiol 28:1737–1746.PubMedCrossRefGoogle Scholar
  14. 14.
    Nadal-Ginard B, Mahdavi V. 1993. Molecular mechanisms of cardiac gene expression. Basic Res Cardiol 88:65–79.PubMedGoogle Scholar
  15. 15.
    Hudlicka O, Brown MD. 1996. Postnatal growth of the heart and its blood vessels. J Vasc Res 33:266–287.PubMedCrossRefGoogle Scholar
  16. 16.
    Rudolph AM. 1979. Fetal and neonatal pulmonary circulation. Ann Review Physiol 41:383–395.CrossRefGoogle Scholar
  17. 17.
    Anversa P, Ricci R, Olivetti G. 1986. Quantitative structural analysis of the myocardium during physiologic growth and induced cardiac hypertrophy: A review. J Amer Coll Cardiol 7:1140–1149.CrossRefGoogle Scholar
  18. 18.
    Dowell RT, McManus RE. 1978. Pressure-induced cardiac enlargement in neonatal and adult rats: Left ventricular functional characteristics and evidence of cardiac muscle cell proliferation in the neonate. Circ Res 42:303–310.PubMedCrossRefGoogle Scholar
  19. 19.
    Anversa P, Olivetti G, Loud AV. 1980. Morphometric study of early postnatal development in the left and right ventricular myocardium of the rat. I. Hypertrophy, hyperplasia, and binucleation of myocytes. Circ Res 46:495–502.PubMedCrossRefGoogle Scholar
  20. 20.
    Anversa P, Palackal T, Sonnenblick EH, Olivetti G, Meggs LG, Capasso JM. 1990. Myocyte cell loss and myocyte cellular hyperplasia in the hypertrophied aging rat heart. Circ Res 67:871–885.PubMedCrossRefGoogle Scholar
  21. 21.
    Olivetti G, Capasso JM, Meggs LG, Sonnenblick EH, Anversa P. 1991. Cellular basis of chronic ventricular remodeling after myocardial infarction in rats. Circ Res 68:856–869.PubMedCrossRefGoogle Scholar
  22. 22.
    Komuro I, Kurabayshi M, Takaku F, Yazaki Y. 1988. Expression of cellular oncogenes in the myocardium during the developmental stage and pressure-overload hypertrophy of the rat. Circ Res 62:1075–1079.PubMedCrossRefGoogle Scholar
  23. 23.
    Lee YA, Liang CS, Lee MA, Lindpaintner K. 1996. Local stress, not systemic factors, regulates gene expression of the cardiac renin-angiotensin system in vivo: A comprehensive study of all its components in the dog. Proc Natl Acad Sci USA 93:11035–11040.PubMedCrossRefGoogle Scholar
  24. 24.
    Shunkert H, Dzau VJ, Tang SS, Hirsh AT, Apstein CS, Lorell BH. 1990. Increased rat cardiac angiotensin converting enzyme activity and mRNA expression in pressure overload left ventricular hypertrophy; Effects on coronary resistance, contractility, and relaxation. J Clin Invest 86:1913–1920.CrossRefGoogle Scholar
  25. 25.
    Aceto JF, Baker KM. 1990. [Sar1]angiotensin II receptor-mediated stimulation of protein synthesis in chick heart cells. Am J Physiol 258.H806–H813.PubMedGoogle Scholar
  26. 26.
    Brilla CG. 1992. Angiotensin II type 2 receptor mediated stimulation of collagen synthesis in human cardiac fibroblasts. Circulation 86:189.Google Scholar
  27. 27.
    Sadoshima J, Xu Y, Slayter HS, Izumo S. 1993. Autocrine release of angiotensin II mediates stretch-induced hypertrophy of cardiac myocytes in vitro. Cell 75:977–984.PubMedCrossRefGoogle Scholar
  28. 28.
    Kijima K, Matsubara H, Murasawa S, Maruyama K, Mori Y, Ohkubo N, Komuro I, Yazaki Y, Iwasaka T, Inada M. 1996. Mechanical stretch induces enhanced expression of angiotensin II receptor subtypes in neonatal rat cardiac myocytes. Circ Res 79:887–897.PubMedCrossRefGoogle Scholar
  29. 29.
    Matsubara H, Kanasaki M, Murasawa S, Tsukaguchi Y, Nio Y, Inada M. 1994. Differential gene expression and regulation of angiotensin II receptor subtypes in rat cardiac fibroblasts and cardiomyocytes in culture. J Clin Invest 93:1592–1601.PubMedCrossRefGoogle Scholar
  30. 30.
    Wong PC, Hart SD, Zasbel AM, Chiu AT, Ardeky RJ, Smith RD, Timmermans PBMWM. 1990. Functional studies of nonpeptide angiotensin II receptor subtype-specific ligands; DuP 753 (All-1) and PD123177 (AU-2). J Pharmcol Exp Ther 255:584–592.Google Scholar
  31. 31.
    Timmermans PBMWM, Wong PC, Chiu AT, Herblin WF. 1991. Nonpeptide angiotensin II receptor antagonists. TIPS 12:55–62.PubMedGoogle Scholar
  32. 32.
    Bumpus FM, Catt KJ, Chiu AT, de Gasparo M, Goodfriend T, Husain A, Peach MJ, Taylor DJ Jr, Timmermans PBMWM. 1991. Nomenclature of angiotensin receptors. A report of the Nomenclature Committee of the Council for High Blood Pressure Research. Hypertension 17:720–721.PubMedCrossRefGoogle Scholar
  33. 33.
    Catt K, Abbott A. 1991. Molecular cloning of angiotensin II receptors may presage further receptor subtypes. TIPS 12:279–281.PubMedGoogle Scholar
  34. 34.
    Millan M, Carvallo P, Izumi SI, Zemel S, Catt KJ, Aguilera G. 1989. Novel sites of functional angiotensin II receptors in the late gestational fetus. Science 244:1340–1342.PubMedCrossRefGoogle Scholar
  35. 35.
    Murphy TJ, Takeuchi K, Alexander RW. 1992. Molecular cloning of AT1 angiotensin receptors. Am J Hypertension 5:236S–242S.Google Scholar
  36. 36.
    Iwai N, Inagami T. 1992. Identification of two subtypes in the rat type I angiotensin II receptor. FEBS Letters 298:257–260.PubMedCrossRefGoogle Scholar
  37. 37.
    Sechi LA, Griffin CA, Grady EF, Kalinyak JE, Schambelan M. 1992. Characterization of angiotensin II receptor subtypes in rat heart. Circ Res 71:1482–1489.PubMedCrossRefGoogle Scholar
  38. 38.
    Rogers TB, Gaa ST, Allen IS. 1986. Identification and characterization of functional angiotensin II receptors on cultured heart myocytes. J Pharmacol Exp Therap 236:438–444.Google Scholar
  39. 39.
    Schorb W, Booz GW, Dostal DE, Conrad KM, Chang KC, Baker KM. 1993. Angiotensin II is mitogenic in neonatal rat cardiac fibroblasts. Circ Res 72:1245–1254.PubMedCrossRefGoogle Scholar
  40. 40.
    Peach MJ, Dostal DE. 1990. The angiotensin II receptor and the actions of angiotensin II. J Cardiovasc Pharmacol 16:S25–S30.PubMedCrossRefGoogle Scholar
  41. 41.
    Dostal DE, Baker KM. 1993. Evidence for a role of an intracardiac renin-angiotensin system in normal and failing hearts. Trends Cardiovas Med 3:67–74.CrossRefGoogle Scholar
  42. 42.
    Hayashida W, Horiuchi M, Dzau VJ. 1996. Intracellular third loop domain of angiotensin II type-2 receptor. J Biol Chem 271:21985–21992.PubMedCrossRefGoogle Scholar
  43. 43.
    Nahmia C, Cazaubon SM, Briend-Sutren MM, Larard D, Billageois P, Strosberg AD. 1995. Angiotensin II AT2 receptors are functionally coupled to protein tyrosine dephosphorylation in N1E-115 neuroblastoma cells. Biochem J 306:87–92.Google Scholar
  44. 44.
    Takashi K, Bardhan S, Kambayashi Y, Shirai H, Inagami T. 1993. Protein tyrosine phosphatase inhibition by angiotensin II in rat pheochromocytoma cells through type 2 receptor, AT2. Biochem Biophys Res Commun 198:60–66.CrossRefGoogle Scholar
  45. 45.
    Taber LA, Pexieder HN, Clark EB, Keller BB. 1993. Residual strain in the ventricle of the stage 16-24 chick embryo, Circ Res 72:455–462.PubMedCrossRefGoogle Scholar
  46. 46.
    Lin CC, Baker KM, Rothblum KN, Booz GW, Dostal DE. 1995. Atrial natriuretic peptide regulation of renin and angiotensinogen mRNA in cultured neonatal rat ventricular cardiac fibroblasts. Hypertension 26:562.CrossRefGoogle Scholar
  47. 47.
    Dostal DE, Rothblum KN, Lin CC, Baker KM. 1995. Regulation of renin and angiotensinogen in cultured neonatal rat cardiac fibroblasts by adrenergic, glucocorticoid, and angiotensin II stimulation. Hypertension 26:562.Google Scholar
  48. 48.
    Dostal DE, Kempinski AM, Hunt RA, Baker KM. 1996. Regulation of renin and angiotensinogen mRNA expression by atrial natriuretic peptide and angiotensin II in cultured neonatal rat cardiac fibroblasts. Hypertension 28:533.Google Scholar
  49. 49.
    Dostal DE, Rothblum TR, Baker KM. 1994. An improved multiplex quantitative polymerase chain reaction: Detection of renin and angiotensinogen mRNA levels in neonate and adult tissue. Anal Biochem 223:239–250.PubMedCrossRefGoogle Scholar
  50. 50.
    Everett AD, Heller F, Fisher A. 1996. AT1 receptor gene regulation in cardiac myocytes and fibroblasts. J Mol Cell Cardiol 28:1727–1736.PubMedCrossRefGoogle Scholar
  51. 51.
    Grady EF, Sechi LA, Griffin CA, Schambelan M, Kalinyak JE. 1991. Expression of AT2 receptors in the developing rat fetus. J Clin Invest 88:921–933.PubMedCrossRefGoogle Scholar
  52. 52.
    Sechi LA, Griffin CA, Grady EF, Kalinyak JE, Schambelan M. 1992. Characterization of angiotensin II receptor subtypes in rat heart. Circ Res 71:1482–1489.PubMedCrossRefGoogle Scholar
  53. 53.
    Hanssens M, Keirse MJNC, Vankelecom F, van Assche FA. 1991. Fetal and neonatal effects of treatment with angiotensin converting enzyme inhibitors in pregnancy. Obstetrics and Gynecol 78:128–135.Google Scholar
  54. 54.
    Erdos EG, Skidgel RA. 1986. The unusual substrate and the distribution of human angiotensin I converting enzyme. Hypertension 8:134–137.Google Scholar
  55. 55.
    Shanmugan S, Corvol P, Gasc JM. 1996. Angiotensin II type 2 receptor mRNA expression in the developing cardiopulmonary system of the rat. Hypertension 28:91–97.CrossRefGoogle Scholar
  56. 56.
    Clubb FJ, Bishop SP. 1984. Formation of binucleated myocardial cells in the neonatal rat; An index for growth hypertrophy. Lab Invest 50:571–577.PubMedGoogle Scholar
  57. 57.
    Nakajima M, Hutchinson HG, Fujinaga M, Hayashida W, Morishita R, Zhang L, Horiuchi M, Pratt RE, Dzau VJ. 1995. The angiotensin II type 2 (AT2) receptor antagonizes the growth effects of the AT1 receptor: Gain-of-function study using gene transfer. Proc Natl Acad Sci USA 92:10663–10667.PubMedCrossRefGoogle Scholar
  58. 58.
    Kirby RF, McCarty R. 1987 Ontogeny of functional sympathetic innervation to the heart and adrenal medulla in the preweanling rat. J Autonom Nerv Sys 19:67–75.CrossRefGoogle Scholar
  59. 59.
    Tucker DC. 1985. Components of functional sympathetic control of heart rate in neonatal rats. Am J Physiol 248:R601–R610.PubMedGoogle Scholar
  60. 60.
    Dostal DE, Rothblum KC, Chernin MI, Cooper GR, Baker KM. 1992. Intracardiac detection of angiotensinogen and renin: Evidence for a localized renin-angiotensin system in neonatal rat heart. Am J Physiol 263:C838–C850.PubMedGoogle Scholar
  61. 61.
    Javadi F, Koke J. 1993. The angiotensin receptor (AT1) inhibitor, losartan, slows postnatal thickening of the left ventricle. Mol Biol Cell (Suppl)4:444a.Google Scholar
  62. 62.
    Beinlich CJ, Baker KM, White GJ, Morgan HE. 1991. Control of growth in the neonatal pig heart. Am J Physiol 261:3–7.PubMedGoogle Scholar
  63. 63.
    Beinlich CJ, White CJ, Baker KM, Morgan HE. 1991. Angiotensin II and left ventricular growth in newborn pig heart. J Mol Cell Cardiol 23:1031–1038.PubMedCrossRefGoogle Scholar
  64. 64.
    Baker KM, Aceto JF. 1990. Angiotensin II stimulation of protein synthesis and cell growth in chick heart cells. Am J Physiol 259:H610–H618.PubMedGoogle Scholar
  65. 65.
    Potts JD, Runyan RB. 1989. Epithelial-mesenchymal cell transformation in the embryonic heart can be mediated, in part, by transforming growth factor β. Dev Biol 134:392–401.PubMedCrossRefGoogle Scholar
  66. 66.
    Bhat GJ, Thekkumkara TJ, Thomas WG, Conrad KM, Baker KM. 1994. Angiotensin II stimulates sis-inducing factor-like DNA binding activity. Evidence that the AT1A receptor activates transcription factor-Stat91 and/or a related protein. J Biol Chem 269:31443–31449.PubMedGoogle Scholar
  67. 67.
    Hunt RA, McWhinney CD, Dostal DE, Baker KM. 1996. Stretch of cardiac myocytes induces sis-inducing factor (SIF)-like DNA binding activity: Evidence for mediation by angiotensin II, Hypertension 28:533.Google Scholar
  68. 68.
    McWhinney CD, Hunt RA, Dostal DE, Baker KM. 1996. Angiotensin II stimulates the STAT signaling pathway in neonatal rat cardiomyocytes. Hypertension 28:511.Google Scholar
  69. 69.
    Ihle JN. 1995. Cytokine receptor signaling. Nature 377:591–594.PubMedCrossRefGoogle Scholar
  70. 70.
    Yan R, Small S, Desplan C, Dearolf C, Darnell JE Jr. 1996. Identification of a Stat gene that functions in Drosophila development. Cell 84:421–430.PubMedCrossRefGoogle Scholar
  71. 71.
    Hou X, Melnick MB, Perrimon N. 1996. Marelle acts downstream of the Drosophila HOP/JAK kinase and encodes a protein similar to mammalian STATS. Cell 84:411–419.PubMedCrossRefGoogle Scholar
  72. 72.
    Hirota H, Yoshida K, Kishimoto T, Taga T. 1995. Continuous activation of gpl30, a signal-transducing receptor component for interleukin 6-related cytokines, causes myocardial hypertrophy in mice. Proc Natl Acad Sci USA 9295:4862–4866.CrossRefGoogle Scholar
  73. 73.
    Yamada T, Horiuchi M, Dzau VJ. 1996. Angiotensin II type 2 receptor mediates programmed cell death. Proc Natl Acad Sci USA 93:156–160.PubMedCrossRefGoogle Scholar
  74. 74.
    Kajstura J, Mansukhani W, Cheng W, Reiss K, Krajewski S, Reed JC, Quaini F, Sonnenblick EH, Anversa P. 1995. Programmed cell death and expression of the protooncogene bcl-2 in myocytes during postnatal maturation of the heart. Exp Cell Res 219:110–121.PubMedCrossRefGoogle Scholar
  75. 75.
    Sadoshima JI, Izumo S. 1993. Molecular characterization of angiotensin II-induced hypertrophy of cardiac myocytes and hyperplasia of cardiac fibroblasts: Critical role of the AT1 receptor subtype. Circ Res 93:413–423.CrossRefGoogle Scholar
  76. 76.
    Lin CL, Baker KM, Thekumkarra TJ, Dostal DE. 1995. A novel biological assay for the rapid detection and quantification of angiotensin II in tissue culture medium. Biotechniques 18:1014–1018.PubMedGoogle Scholar
  77. 77.
    Cheng W, Li B, Kajstura J, Li P, Wolin MS, Sonnenblick EH, Hintze The, Olivetti G, Anversa P. 1995. Stretch-induced programmed myocyte cell death. J Clin Invest 96:2247–2259.PubMedCrossRefGoogle Scholar
  78. 78.
    Zhang X, Dostal DE, Reiss K, Cheng W, Kajstura J, Li P, Huang H, Sonnenblick EH, Meggs LG, Baker KM, Anversa P. 1995. Identification and activation of the autocrine renin-angiotensin system in adult ventricular myocytes in vivo. Am J Physiol 269:H1791–H1802.PubMedGoogle Scholar
  79. 79.
    Anversa P, Zhang X, Li P, Capasso JM. 1992. Chronic coronary artery constriction leads to moderate myocyte loss and left ventricular dysfunction and failure in rats. J Clin Invest 89:618–629.PubMedCrossRefGoogle Scholar
  80. 80.
    Cheng W, Kajstura J, Nitahara JA, Li B, Reiss K, Liu Y, Clark WA, Krajewski S, Reed JC, Olivetti G, Anversa P 1996. Programmed myocyte cell death affects the viable myocardium after infarction in rats. Exp Cell Res 226:316–327.PubMedCrossRefGoogle Scholar
  81. 81.
    Oltvai ZN, Milliman CL, Korsmeyer SJ. 1993. Bcl-2 heterodimerizes in vivo with a conserved homologue, Bax, that accelerates programmed cell death. Cell 74:609–619.PubMedCrossRefGoogle Scholar
  82. 82.
    Horiuchi M, Hayashida W, Yamada T, Dzau VJ. 1996. Angiotensin type 2 receptor dephosphory-lates Bcl-2 by activating mitogen-activated protein kinase phosphatase-1 and induces apoptosis. Hypertension 28:531.Google Scholar
  83. 83.
    Rogg H, Schmid A, de Gasparo M. 1990. Identification and characterization of angiotensin II receptor subtypes in rabbit ventricular myocardium. Biochem Biophys Res Commun 173:416–422.PubMedCrossRefGoogle Scholar
  84. 84.
    Allen AM, Yamada H, Mendelsohn FAO. 1990. Iv vitro autoradiographic localization of binding to angiotensin receptors in the rat heart. Int J Cardiol 28:25–33.PubMedCrossRefGoogle Scholar
  85. 85.
    Lindner KH, Pregnel AW, Pfenninger EG, Lindner IM. 1995. Angiotensin II augments reflex activity of the sympathetic nervous system during cardiopulmonary resuscitation in pigs. Circulation 92:1020–1025.PubMedCrossRefGoogle Scholar
  86. 86.
    Osterziel KJ, Hanlein D, Dietz R. 1994. Interactions between the renin-angiotensin system and the parasympathetic nervous system in heart failure. J Cardiovasc Pharm 24:S70–S74.Google Scholar
  87. 87.
    Suzuki J, Matsubara H, Urakami M, Inada M. 1993. Rat angiotensin II (type 1A) receptor mRNA regulation and subtype expression in myocardial growth and hypertrophy. Circ Res 73:439–447.PubMedCrossRefGoogle Scholar
  88. 88.
    Heymes C, Swynghedauw B, Chevailer B. Activation of angiotensinogen and angiotensin-converting enzyme gene expression in the left ventricle of senescent rats. Circulation 90:1328–1333.Google Scholar
  89. 89.
    Kim HS, Krege JH, Kluckman KD, Hagaman JR, Hodgin JB, Best CF, Jennette JC, Coffman TM, Maeda N, Smithies O. 1995. Genetic control of blood pressure and the angiotensinogen locus. Proc Natl Acad Sci USA 92:2735–2739.PubMedCrossRefGoogle Scholar
  90. 90.
    Ito M, Oliverio MI, Mannon PJ, Best CF, Maeda N, Smithies O, Cofrman TM. 1995. Regulation of blood pressure by the type 1A angiotensin II receptor gene, Proc Natl Acad Sci USA 92:3521–3535.PubMedCrossRefGoogle Scholar
  91. 91.
    Nimura F, Labosky PA, Kakuchi J, Okubo S, Yoshida H, Oikawa T, Ichiki T, Naftilan AJ, Fogo A, Inagami T. 1995. Gene targeting in mice reveals a requirement for angiotensin in the development and maintenance of kidney morphology and growth factor regulation. J Clin Invest 96:2947–2954.CrossRefGoogle Scholar
  92. 92.
    Ichiki T, Labosky PA, Shiota C, Okuyama S, Imagawa Y, Fogo A, Niimura F, Ichikawa I, Hogan BL, Inagami T. 1995. Effects on blood pressure and exploratory behaviour of mice lacking angiotensin II type-2 receptors. Nature 377:748–750.PubMedCrossRefGoogle Scholar
  93. 93.
    Hein L, Barsh GS, Pratt RE, Dzau VJ, Kobilka BK. 1995. Behavioural and cardiovascular effects of disrupting the angiotensin II type-2 receptor in mice. Nature 377:744–747.PubMedCrossRefGoogle Scholar
  94. 94.
    Hoffman JI. 1995. Incidence of congenital heart disease: I. Postnatal incidence. Ped Cardiol 16:103–113.CrossRefGoogle Scholar
  95. 95.
    Hofrman JI. 1995. Incidence of congenital heart disease: II. Prenatal incidence. Ped Cardiol 16:155–165.Google Scholar

Copyright information

© Springer Science+Business Media New York 1998

Authors and Affiliations

  • David E. Dostal
    • 1
  • Rachel A. Hunt
    • 1
  • Chris E. Kule
    • 1
  • Kenneth M. Baker
    • 1
  1. 1.Weis Center for ResearchGeisinger ClinicDanvilleUSA

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