Cellular and Molecular Aspects of the A-Type Natriuretic Peptide

  • David G. Gardner
  • Jianming Wu
  • Branka Kovacic-Milivojevic
Part of the Contemporary Endocrinology book series (COE, volume 5)


Physiologists have long suspected that the cardiac atria play an important role in the regulation of intravascular volume and blood pressure. The first suggestive evidence that these structures might function as endocrine organs came from the studies of Kisch (1) that demonstrated the presence of membrane-bound secretory granules within atrial myocytes, a finding that was confirmed in the studies of Jamison and Palade (2) several years later. In 1981 DeBold et al. (3) demonstrated that extracts from atrial, but not ventricular, tissue effected a pronounced natriuresis in test animals. The active component of these extracts, the natriuretic factor or natriuretic peptides, as they are now known, immediately attracted the interest of physiologists, pharmacologists, cell and molecular biologists, and clinicians, reflecting their broad-based physiological effects, novel signal-transduction mechanisms, and potential therapeutic utility. This chapter will focus on the cell and molecular biology of the atrial, or A-type, natriuretic peptide. Where appropriate, efforts will be made to contrast and/or integrate these findings with those obtained for other members of the natriuretic peptide family.


Brain Natriuretic Peptide Atrial Natriuretic Peptide Atrial Natriuretic Factor Atrial Myocytes Chloramphenicol Acetyl Transferase 
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  1. 1.
    Kisch B. Electron microscopy of the atrium of the heart. I. Guinea pig. Exp Med Surg 1956;14:99–112.PubMedGoogle Scholar
  2. 2.
    Jamison JD, Palade GE. Specific granules in atrial muscle cells. J Cell Biol 1964;23:151–172.CrossRefGoogle Scholar
  3. 3.
    de Bold AJ, Borenstein HB, Veress AT, Sonnenberg H. A rapid and potent natriuretic response to intravenous injection of atrial myocardial extract in rats. Life Sci 1981;28:89–94.PubMedCrossRefGoogle Scholar
  4. 4.
    Maki M, Takayanagi R, Misono KS, Pandey KN, Tibbetts C, Inagami T. Structure of rat atrial natriuretic factor precursor deduced from cDNA sequence. Nature 1984;309:722–724.PubMedCrossRefGoogle Scholar
  5. 5.
    Yamanaka M, Greenberg B, Johnson L, Seilhamer J, Brewer M, Friedemann T, Miller J, Atlas S, Laragh J, Lewicki J, et al. Cloning and sequence analysis of the cDNA for the rat atrial natriuretic factor precursor. Nature 1984;309:719–722.PubMedCrossRefGoogle Scholar
  6. 6.
    Zivin RA, Condra JH, Dixon RA, Seidah NG, Chretien M, Nemer M, Chamberland M, Drouin J. Molecular cloning and characterization of DNA sequences encoding rat and human atrial natriuretic factors. Proc Natl Acad Sci USA 1984;81:6325–6329.PubMedCrossRefGoogle Scholar
  7. 7.
    Flynn TG, Davies PL, Kennedy BP, de Bold ML, de Bold AJ. Alignment of rat cardionatrin sequences with the preprocardionatrin sequence from complementary DNA. Science 1985;228:323–325.PubMedCrossRefGoogle Scholar
  8. 8.
    Kangawa K, Tawaragi Y, Oikawa S, Mizuno A, Sakuragawa Y, Nakazato H, Fukuda A, Minamino N, Matsuo H. Identification of rat gamma atrial natriuretic polypeptide and characterization of the cDNA encoding its precursor. Nature 1984;312:152–155.PubMedCrossRefGoogle Scholar
  9. 9.
    Seidman CE, Duby AD, Choi E, Graham RM, Haber E, Homcy C, Smith JA, Seidman JG. The structure of rat preproatrial natriuretic factor as defined by a complementary DNA clone. Science 1984;225:324–326.PubMedCrossRefGoogle Scholar
  10. 10.
    Nakayama K, Ohkubo H, Hirose T, Inayama S, Nakanishi S. mRNA sequence for human cardiodilatin-atrial natriuretic factor precursor and regulation of precursor mRNA in rat atria. Nature 1984;310:699–701.PubMedCrossRefGoogle Scholar
  11. 11.
    Oikawa S, Imai M, Ueno A, Tanaka S, Noguchi T, Nakazato H, Kangawa K, Fukuda A, Matsuo H. Cloning and sequence analysis of cDNA encoding a precursor for human atrial natriuretic polypeptide. Nature 1984;309:724–726.PubMedCrossRefGoogle Scholar
  12. 12.
    Oikawa S, Imai M, Inuzuka C, Tawaragi Y, Nakazato H, Matsuo H. Structure of dog and rabbit precursors of atrial natriuretic polypeptides deduced from nucleotide sequence of cloned cDNA. Biochem Biophys Res Commun 1985;132:892–899.PubMedCrossRefGoogle Scholar
  13. 13.
    Argentin S, Nemer M, Drouin J, Scott GK, Kennedy BP, Davies PL. The gene for rat atrial natriuretic factor. J Biol Chem 1985;260:4568–4571.PubMedGoogle Scholar
  14. 14.
    Maki M, Parmentier M, Inagami T. Cloning of genomic DNA for human atrial natriuretic factor. Biochem Biophys Res Commun 1984;125:797–802.PubMedCrossRefGoogle Scholar
  15. 15.
    Seidman CE, Bloch KD, Klein KA, Smith JA, Seidman JG. Nucleotide sequences of the human and mouse atrial natriuretic factor genes. Science 1984;226:1206–1209.PubMedCrossRefGoogle Scholar
  16. 16.
    Greenberg BD, Bencen GH, Seilhamer JJ, Lewicki JA, Fiddes JC. Nucleotide sequence of the gene encoding human atrial natriuretic factor precursor. Nature 1984;312:656–658.PubMedCrossRefGoogle Scholar
  17. 17.
    Nemer M, Chamberland M, Sirois D, Argentin S, Drouin J, Dixon RA, Zivin RA, Condra JH. Gene structure of human cardiac hormone precursor, pronatriodilatin. Nature 1984;312:654–656.PubMedCrossRefGoogle Scholar
  18. 18.
    Vlasuk GP, Miller J, Bencen GH, Lewicki JA. Structure and analysis of the bovine atrial natriuretic peptide precursor gene. Biochem Biophys Res Commun 1986;136:396–403.PubMedCrossRefGoogle Scholar
  19. 19.
    Dracopoli NC, Stanger BZ, Ito CY, Call KM, Lincoln SE, Lander ES, Housman DE. A genetic linkage map of 27 loci from PND to FY on the short arm of human chromosome I. Am J Hum Genet 1988;43:462–470.PubMedGoogle Scholar
  20. 20.
    Yang-Feng TL, Floyd-Smith G, Nemer M, Drouin J, Francke U. The pronatriodilatin gene is located on the distal short arm of human chromosome 1 and on mouse chromosome 4. Am J Hum Genet 1985;37:1117–1128.PubMedGoogle Scholar
  21. 21.
    Mullins JJ, Zeng Q, Gross KW. Mapping of the mouse atrial natriuretic factor gene. Evidence for tight linkage to the Fv-1 locus. Hypertension 1987;9:518–521.PubMedGoogle Scholar
  22. 22.
    Kobayashi E, Tachibana M, Ikadai H, Kunieda T. A genetic linkage map of rat chromosome 5 reveals extensive linkage conservation with mouse chromosome 4. Mamm Genome 1994;5:222–224.PubMedCrossRefGoogle Scholar
  23. 23.
    Deng AY, Dene H, Pravenec M, Rapp JP. Genetic mapping of two new blood pressure quantitative trait loci in the rat by genotyping endothelin system genes. J Clin Invest 1994;93:2701–2709.PubMedCrossRefGoogle Scholar
  24. 24.
    Serikawa T, Kuramoto T, Hilbert P, Mori M, Yamada J, Dubay CJ, Lindpainter K, Ganten D, Guenet JL, Lathrop GM, et al. Rat gene mapping using PCR-analyzed microsatellites. Genetics 1992; 131:701–721.PubMedGoogle Scholar
  25. 25.
    Szpirer C, Riviere M, Szpirer J, Genet M, Dreze P, Islam MQ, Levan G. Assignment of 12 loci to rat chromosome 5: evidence that this chromosome is homologous to mouse chromosome 4 and to human chromosomes 9 and 1 (lp arm). Genomics 1990;6:679–684.PubMedCrossRefGoogle Scholar
  26. 26.
    Nemer M, Sirois D, Drouin J. TaqI polymorphism at the 3’ end of the human pronatriodilatin gene (hPND). Nucleic Acids Res 1986;14:8697.PubMedCrossRefGoogle Scholar
  27. 27.
    Frossard PM, Coleman RT. Human atrial natriuretic peptides (ANP) gene locus: BglI RFLP. Nucleic Acids Res 1986;14:9223.PubMedCrossRefGoogle Scholar
  28. 28.
    Nemer M, Sirois D, Drouin J. Xhol polymorphism at the human pronatriodilatin (hPND) gene locus. Nucleic Acids Res 1986;14:8696.PubMedCrossRefGoogle Scholar
  29. 29.
    Steinhelper ME. Structure, expression, and genomic mapping of the mouse natriuretic peptide type-B gene. Circ Res 1993;72:984–992.PubMedGoogle Scholar
  30. 30.
    Arden KC, Viars CS, Weiss S, Argentin S, Nemer M. Localization of the human B-type natriuretic peptide precursor (NPPB) gene to chromosome lp36. Genomics 1995;26:385–389.PubMedCrossRefGoogle Scholar
  31. 31.
    Gardner DG, Deschepper CF, Ganong WF, Hane S, Fiddes J, Baxter JD, Lewicki J. Extra-atrial expression of the gene for atrial natriuretic factor. Proc Natl Acad Sci U S A 1986;83:6697–6701.PubMedCrossRefGoogle Scholar
  32. 32.
    Zeller R, Bloch KD, Williams BS, Arceci RJ, Seidman CE. Localized expression of the atrial natriuretic factor gene during cardiac embryogenesis. Genes Dev 1987;1:693–698.PubMedCrossRefGoogle Scholar
  33. 33.
    Kikuchi K, Nakao K, Hayashi K, Morii N, Sugawara A, Sakamoto M, Imura H, Mikawa H. Ontogeny of atrial natriuretic polypeptide in the human heart. Acta Endocrinol (Copenh) 1987; 115:211–217.PubMedGoogle Scholar
  34. 34.
    Wei YF, Rodi CP, Day ML, Wiegand RC, Needleman LD, Cole BR, Needleman P. Developmental changes in the rat atriopeptin hormonal system. J Clin Invest 1987;79:1325–1329.PubMedCrossRefGoogle Scholar
  35. 35.
    Wu JP, Deschepper CF, Gardner DG. Perinatal expression of the atrial natriuretic factor gene in rat cardiac tissue. Am J Physiol 1988;255:E388–396.PubMedGoogle Scholar
  36. 36.
    Claycomb WC. Atrial-natriuretic-factor mRNA is developmentally regulated in heart ventricles and actively expressed in cultured ventricular cardiac muscle cells of rat and human. Biochem J 1988;255:617–620.PubMedGoogle Scholar
  37. 37.
    Gardner DG, Hedges BK, Wu J, LaPointe MC, Deschepper CF. Expression of the atrial natriuretic peptide gene in human fetal heart. J Clin Endocrinol Metab 1989;69:729–737.PubMedCrossRefGoogle Scholar
  38. 38.
    Camreon VA, Aitken GD, Ellmers LJ, Kennedy MA, Espiner EA. The sites of gene expression of atrial, brain, and C-type natriuretic peptides in mouse fetal development: temporal changes in embryos and placenta. Endocrinology 1996;137:817–824.CrossRefGoogle Scholar
  39. 39.
    Day ML, Schwartz D, Wiegand RC, Stockman PT, Brunnert SR, Tolunay HE, Currie MG, Standaert DG, Needleman P. Ventricular atriopeptin. Unmasking of messenger RNA and peptide synthesis by hypertrophy or dexamethasone. Hypertension 1987;9:485–191.PubMedGoogle Scholar
  40. 40.
    Lee RT, Bloch KD, Pfeffer JM, Pfeffer MA, Neer EJ, Seidman CE. Atrial natriuretic factor gene expression in ventricles of rats with spontaneous biventricular hypertrophy. J Clin Invest 1988;81:431–434.PubMedCrossRefGoogle Scholar
  41. 41.
    Saito Y, Nakao K, Arai H, Nishimura K, Okumura K, Obata K, Takemura G, Fujiwara H, Sugawara A, Yamada T, et al. Augmented expression of atrial natriuretic polypeptide gene in ventricle of human failing heart. J Clin Invest 1989;83:298–305.PubMedCrossRefGoogle Scholar
  42. 42.
    Gu J, D’Andrea M, Seethapathy M. Atrial natriuretic peptide and its messenger ribonucleic acid in overloaded and overload-released ventricles of rat. Endocrinology 1989;125:2066–2074.PubMedCrossRefGoogle Scholar
  43. 43.
    Saper CB, Standaert DG, Currie MG, Schwartz D, Geller DM, Needleman P. Atriopeptin-immunore-active neurons in the brain: presence in cardiovascular regulatory areas. Science 1985;227:1047–1049.PubMedCrossRefGoogle Scholar
  44. 44.
    Gardner DG, Vlasuk GP, Baxter JD, Fiddes JC, Lewicki JA. Identification of atrial natriuretic factor gene transcripts in the central nervous system of the rat. Proc Natl Acad Sci USA 1987;84:2175–2179.PubMedCrossRefGoogle Scholar
  45. 45.
    Gundlach AL, Knobe ICE. Distribution of preproatrial natriuretic peptide mRNA in rat brain detected by in situ hybridization of DNA oligonucleotides: enrichment in hypothalamic and limbic regions. J Neurochem 1992;59:758–761.PubMedCrossRefGoogle Scholar
  46. 46.
    Gardner DG, Deschepper CF, Baxter JD. The gene for the atrial natriuretic factor is expressed in the aortic arch. Hypertension 1987;9:103–106.PubMedGoogle Scholar
  47. 47.
    McKenzie JC, Tanaka I, Misono KS, Inagami T. Immunocytochemical localization of atrial natriuretic factor in the kidney, adrenal medulla, pituitary, and atrium of rat. J Histochem Cytochem 1985;33:828–832.PubMedCrossRefGoogle Scholar
  48. 48.
    Golomb E, Friedman E, Abassi ZA, Trachewsky D, Keiser HR. Rare renal transcription of the atrial natriuretic factor gene in rats. Demonstration by polymerase chain reaction. Am J Hypertens 1993;6:867–872.PubMedGoogle Scholar
  49. 49.
    Greenwald JE, Ritter D, Tetens E, Rotwein PS. Renal expression of the gene for atrial natriuretic factor. Am J Physiol 1992;263:F974–978.PubMedGoogle Scholar
  50. 50.
    Ritter D, Chao J, Needleman P, Tetens E, Greenwald JE. Localization, synthetic regulation, and biology of renal atriopeptin-like prohormone. Am J Physiol 1992;263:F503–509.PubMedGoogle Scholar
  51. 51.
    Morel G, Chabot JG, Gossard F, Heisler S. Is atrial natriuretic peptide synthesized and internalized by gonadotrophs? Endocrinology 1989;124:1703–1710.PubMedCrossRefGoogle Scholar
  52. 52.
    Vollmar AM, Schulz R. Atrial natriuretic peptide is synthesized in the human thymus. Endocrinology 1990;126:2277–2280.PubMedCrossRefGoogle Scholar
  53. 53.
    Vollmar AM, Wolf R, Schulz R. Co-expression of the natriuretic peptides (ANP, BNP, CNP) and their receptors in normal and acutely involuted rat thymus. J Neuroimmunol 1995;57:117–127.PubMedCrossRefGoogle Scholar
  54. 54.
    Gutkowska J, Nemer M, Sole MJ, Drouin J, Sirois P. Lung is an important source of atrial natriuretic factor in experimental cardiomyopathy. J Clin Invest 1989;83:1500–1504.PubMedCrossRefGoogle Scholar
  55. 55.
    Throsby M, Lee D, Huang WQ, Yang ZY, Copolov DL, Lim AT. Evidence for atrial natriuretic peptide-(5–28) production by macrophages of the rat spleen: an immunochemical and nonradioactive in situ hybridization approach. Endocrinology 1991;129:991–1000.PubMedCrossRefGoogle Scholar
  56. 56.
    Vollmar AM, Schulz R. Expression and differential regulation of natriuretic peptides in mouse macrophages. J Clin Invest 1995;95:2442–2450.PubMedCrossRefGoogle Scholar
  57. 57.
    Wong M, Samson WK, Dudley CA, Moss RL. Direct, neuronal action of atrial natriuretic factor in the rat brain. Neuroendocrinology 1986;44:49–53.PubMedCrossRefGoogle Scholar
  58. 58.
    Standaert DG, Cechetto DF, Needleman P, Saper CB. Inhibition of the firing of vasopressin neurons by atriopeptin. Nature 1987;329:151–153.PubMedCrossRefGoogle Scholar
  59. 59.
    Ermirio R, Ruggeri P, Cogo CE, Molinari C, Calaresu FR. Neuronal and cardiovascular responses to ANF microinjected into the solitary nucleus. Am J Physiol 1989;256:R577–582.PubMedGoogle Scholar
  60. 60.
    Imura H, Nakao K, Itoh H. The natriuretic peptide system in the brain: implications in the central control of cardiovascular and neuroendocrine functions. Front Neuroendocrinol 1992;13:217–249.PubMedGoogle Scholar
  61. 61.
    Volpe M, Cuocolo A, Vecchione F, Mele AF, Condorelli M, Trimarco B. Vagal mediation of the effects of atrial natriuretic factor on blood pressure and arterial baroreflexes in the rabbit. Circ Res 1987;60:747–755.PubMedGoogle Scholar
  62. 62.
    Thoren P, Mark AL, Morgan DA, O’Neill TP, Needleman P, Brody MJ. Activation of vagal depressor reflexes by atriopeptins inhibits renal sympathetic nerve activity. Am J Physiol 1986;251:H1252–1259.PubMedGoogle Scholar
  63. 63.
    Schultz HD, Gardner DG, Deschepper CF, Coleridge HM, Coleridge JC. Vagal C-fiber blockade abolishes sympathetic inhibition by atrial natriuretic factor. Am J Physiol 1988;255:R6–13.PubMedGoogle Scholar
  64. 64.
    Schulz-Knappe P, Forssmann K, Herbst F, Hock D, Pipkorn R, Forssmann WG. Isolation and structural analysis of “urodilatin,” a new peptide of the cardiodilatin-(ANP)-family, extracted from human urine. Klin Wochenschr 1988;66:752–759.PubMedCrossRefGoogle Scholar
  65. 65.
    Valentin JP, Humphreys MH. Urodilatin: a paracrine renal natriuretic peptide. Semin Nephrol 1993;13:61–70.PubMedGoogle Scholar
  66. 66.
    Sonnenberg H, Honrath U, Wilson DR. In vivo microperfusion of inner medullary collecting duct in rats: effect of amiloride and ANF. Am J Physiol 1990;259:F222–226.PubMedGoogle Scholar
  67. 67.
    Seidman CE, Wong DW, Jarcho JA, Bloch KD, Seidman JG. Cis-acting sequences that modulate atrial natriuretic factor gene expression. Proc Natl Acad Sci USA 1988;85:4104–4108.PubMedCrossRefGoogle Scholar
  68. 68.
    Rosenzweig A, Halazonetis TD, Seidman JG, Seidman CE Proximal regulatory domains of rat atrial natriuretic factor gene. Circulation 1991;84:1256–1265.PubMedGoogle Scholar
  69. 69.
    Knowlton KU, Baracchini E, Ross RS, Harris AN, Henderson SA, Evans SM, Glembotski CC, Chien KR. Co-regulation of the atrial natriuretic factor and cardiac myosin light chain-2 genes during alpha-adrenergic stimulation of neonatal rat ventricular cells. Identification of cis sequences within an embryonic and a constitutive contractile protein gene which mediate inducible expression. J Biol Chem 1991;266:7759–7768.PubMedGoogle Scholar
  70. 70.
    LaPointe MC, Wu JP, Greenberg B, Gardner DG. Upstream sequences confer atrial-specific expression on the human atrial natriuretic factor gene. J Biol Chem 1988;263:9075–9078.PubMedGoogle Scholar
  71. 71.
    Wu J, LaPointe MC, West BL, Gardner DG. Tissue-specific determinants of human atrial natriuretic factor gene expression in cardiac tissue. J Biol Chem 1989;264:6472–6479.PubMedGoogle Scholar
  72. 72.
    Wu JP, Kovacic-Milivojevic B, Lapointe MC, Nakamura K, Gardner DG. Cis-active determinants of cardiac-specific expression in the human atrial natriuretic peptide gene. Mol Endocrinol 1991;5:1311–1322.PubMedCrossRefGoogle Scholar
  73. 73.
    McBride K, Robitaille L, Tremblay S, Argentin S, Nemer M. fos/jun repression of cardiac-specific transcription in quiescent and growth-stimulated myocytes is targeted at a tissue-specific cis element. Mol Cell Biol 1993;13:600–612.PubMedGoogle Scholar
  74. 74.
    Argentin S, Ardati A, Tremblay S, Lihrmann I, Robitaille L, Drouin J, Nemer M. Developmental stage-specific regulation of atrial natriuretic factor gene transcription in cardiac cells. Mol Cell Biol 1994;14:777–790.PubMedGoogle Scholar
  75. 75.
    Sartorelli V, Webster KA, Kedes L. Muscle-specific expression of the cardiac alpha-actin gene requires MyoD1, CArG-box binding factor, and Spl. Genes Dev 1990;4:1811–1822.PubMedCrossRefGoogle Scholar
  76. 76.
    Parker TG, Chow KL, Schwartz RJ, Schneider MD. Positive and negative control of the skeletal alpha-actin promoter in cardiac muscle. A proximal serum response element is sufficient for induction by basic fibroblast growth factor (FGF) but not for inhibition by acidic FGF. J Biol Chem 1992;267:3343–3350.PubMedGoogle Scholar
  77. 77.
    MacLellan WR, Lee TC, Schwartz RJ, Schneider MD. Transforming growth factor-beta response elements of the skeletal alpha-actin gene. Combinatorial action of serum response factor, YY1, and the SV40 enhancer-binding protein, TEF-1. J Biol Chem 1994;269:16,754–16,760.Google Scholar
  78. 78.
    Treisman R. Journey to the surface of the cell: Fos regulation and the SRE. EMBO J 1995;14:4905–4913.PubMedGoogle Scholar
  79. 79.
    Sprenkle AB, Murray SF, Glembotski CC. Involvement of multiple cis elements in basal- and alpha-adrenergic agonist-inducible atrial natriuretic factor transcription. Roles for serum response elements and an SP-1–like element. Circ Res 1995;77:1060–1069.PubMedGoogle Scholar
  80. 80.
    Kovacic-Milivojevic B, Zlock DW, Gardner DG. Ras-dependent regulation of hANP gene transcription. 48th Ann Fall Conf and Sci Sess., Council for High Blood Press Res 1994;Abs 9.Google Scholar
  81. 81.
    Grepin C, Dagnino L, Robitaille L, Haberstroh L, Antakly T, Nemer M. A hormone-encoding gene identifies a pathway for cardiac but not skeletal muscle gene transcription. Mol Cell Biol 1994;14:3115–129.PubMedGoogle Scholar
  82. 82.
    Thuerauf DJ, Hanford DS, Glembotski CC. Regulation of rat brain natriuretic peptide transcription. A potential role for GATA-related transcription factors in myocardial cell gene expression. J Biol Chem 1994;269:17,772–17,775.Google Scholar
  83. 83.
    Field LJ. Atrial natriuretic factor-SV40 T antigen transgenes produce tumors and cardiac arrhythmias in mice. Science 1988;239:1029–1033.PubMedCrossRefGoogle Scholar
  84. 84.
    Steinhelper ME, Lanson NA, Dresdner KP, Delcarpio JB, Wit AL, Claycomb WC, Field LJ. Proliferation in vivo and in culture of differentiated adult atrial cardiomyocytes from transgenic mice. Am J Physiol. 1990;259:H1826–H1834.PubMedGoogle Scholar
  85. 85.
    Lanson NA Jr, Glembotski CC, Steinhelper ME, Field LJ, Claycomb WC. Gene expression and atrial natriuretic factor processing and secretion in cultured AT-1 cardiac myocytes. Circulation 1992;85:1835–1841.PubMedGoogle Scholar
  86. 86.
    Kline RP, Sorota S, Dresdner KP, Steinhelper ME, Lanson NA Jr, Wit AL, Claycomb WC, Field LJ. Spontaneous activity in transgenic mouse heart: comparison of primary atrial tumor with cultured AT-1 atrial myocytes. J Cardiovasc Electrophysiol 1993;4:642–660.PubMedCrossRefGoogle Scholar
  87. 87.
    Seidman CE, Schmidt EV, Seidman JG. cis-dominance of rat atrial natriuretic factor gene regulatory sequences in transgenic mice. Can J Physiol Pharmacol 1991;69:1486–1492.PubMedCrossRefGoogle Scholar
  88. 88.
    Knowlton KU, Rockman HA, Itani M, Vovan A, Seidman CE, Chien KR. Divergent pathways mediate the induction of ANF transgenes in neonatal and hypertrophic ventricular myocardium. J Clin Invest 1995;96:1311–1318.PubMedCrossRefGoogle Scholar
  89. 89.
    Gardner DG, Hane S, Trachewsky D, Schenk D, Baxter JD. Atrial natriuretic peptide mRNA is regulated by glucocorticoids in vivo. Biochem Biophys Res Commun 1986;139:1047–1054.PubMedCrossRefGoogle Scholar
  90. 90.
    Dananberg J, Grekin RJ. Corticoid regulation of atrial natriuretic factor secretion and gene expression. Am J Physiol 1992;263:H1377–1381.PubMedGoogle Scholar
  91. 91.
    Gardner DG, Gertz BJ, Deschepper CF, Kim DY. Gene for the rat atrial natriuretic peptide is regulated by glucocorticoids in vitro. J Clin Invest 1988;82:1275–1281.PubMedCrossRefGoogle Scholar
  92. 92.
    Matsubara H, Hirata Y, Yoshimi H, Takata S, Takagi Y, Yamane Y, Umeda Y, Nishikawa M, Inada M. Ventricular myocytes from neonatal rats are more responsive to dexamethasone than atrial myocytes in synthesis of atrial natriuretic peptide. Biochem Biophys Res Commun 1987;148:1030–1038.PubMedCrossRefGoogle Scholar
  93. 93.
    Shields PP, Dixon JE, Glembotski CC. The secretion of atrial natriuretic factor-(99–126) by cultured cardiac myocytes is regulated by glucocorticoids. J Biol Chem 1988;263:12,619–12,628.Google Scholar
  94. 94.
    Argentin S, Sun YL, Lihrmann I, Schmidt TJ, Drouin J, Nemer M. Distal cis-acting promoter sequences mediate glucocorticoid stimulation of cardiac atrial natriuretic factor gene transcription. J Biol Chem 1991;266:23,315–23,322.Google Scholar
  95. 95.
    Mangelsdorf DJ, Thummel C, Beato M, Herrlich P, Schutz G, Umesono K, Blumberg B, Kastner P, Mark M, Chambon P, et al. The nuclear receptor superfamily: the second decade. Cell 1995;83:835–839.PubMedCrossRefGoogle Scholar
  96. 96.
    Wang G, Lim AT. Glucocorticoid stimulation of pro-ANF mRNA expression of adult rat hypothalamic neurons in culture: a cAMP-dependent effect. Endocrinology 1996;137:379–382.PubMedCrossRefGoogle Scholar
  97. 97.
    Deschepper CF, Nguyen KP, Lapointe MC, Zahs KR, Gardner DG. Production and differential endocrine regulation of atrial natriuretic peptide in neuron-enriched primary cultures. Endocrinology 1991;128:5–12.PubMedCrossRefGoogle Scholar
  98. 98.
    Gardner DG, Gertz BJ, Hane S. Thyroid hormone increases rat atrial natriuretic peptide messenger ribonucleic acid accumulation in vivo and in vitro. Mol Endocrinol 1987;1:260–265.PubMedCrossRefGoogle Scholar
  99. 99.
    Ladenson PW, Bloch KD, Seidman JG. Modulation of atrial natriuretic factor by thyroid hormone: messenger ribonucleic acid and peptide levels in hypothyroid, euthyroid, and hyperthyroid rat atria and ventricles. Endocrinology 1988;123:652–657.PubMedCrossRefGoogle Scholar
  100. 100.
    Rundle SE, Fullerton MJ, Funder JW. Induction of ventricular morphogenesis and atrial natriuretic factor synthesis by thyroid hormone. Mol Cell Endocrinol 1990;68:163–168.PubMedCrossRefGoogle Scholar
  101. 101.
    Ballermann BJ, Bloch KD, Seidman JG, Brenner BM. Atrial natriuretic peptide transcription, secretion, and glomerular receptor activity during mineralocorticoid escape in the rat. J Clin Invest 1986;78:840–843.PubMedCrossRefGoogle Scholar
  102. 102.
    Metzler CH, Gardner DG, Keil LC, Baxter JD, Ramsay DJ. Increased synthesis and release of atrial peptide during DOCA escape in conscious dogs. Am J Physiol 1987;252:R188–192.PubMedGoogle Scholar
  103. 103.
    Yokota N, Bruneau BG, Kuroski de Bold ML, de Bold AJ. Atrial natriuretic factor significantly contributes to the mineralocorticoid escape phenomenon. Evidence for a guanylate cyclase-mediated pathway. J Clin Invest 1994;94:1938–1946.PubMedCrossRefGoogle Scholar
  104. 104.
    Wu J, Garami M, Cao L, Li Q, Gardner DG. 1,25(OH)2D3 suppresses expression and secretion of atrial natriuretic peptide from cardiac myocytes. Am J Physiol 1995;268:E1108–1113.PubMedGoogle Scholar
  105. 105.
    Li Q, Gardner DG. Negative regulation of the human atrial natriuretic peptide gene by 1,25–dihydroxyvitamin D3. J Biol Chem 1994;269:4934–4939.PubMedGoogle Scholar
  106. 106.
    Zhou MD, Sucov HM, Evans RM, Chien KR. Retinoid-dependent pathways suppress myocardial cell hypertrophy. Proc Natl Acad Sci USA 1995;92:7391–7395.PubMedCrossRefGoogle Scholar
  107. 107.
    Wu J, Garami M, Cheng T, Gardner DG. 1,25(OH)2 vitamin D3 and retinoic acid antagonize endothelin-stimulated hypertrophy of neonatal rat cardiac myocytes. J Clin Invest 1996;97:1577–1588.PubMedCrossRefGoogle Scholar
  108. 108.
    Sei CA, Irons CE, Sprenkle AB, McDonough PM, Brown JH, Glembotski CC. The alpha-adrenergic stimulation of atrial natriuretic factor expression in cardiac myocytes requires calcium influx, protein kinase C, and calmodulin-regulated pathways. J Biol Chem 1991;266:15,910–15,916.Google Scholar
  109. 109.
    Ardati A, Nemer M. A nuclear pathway for alpha 1–adrenergic receptor signaling in cardiac cells. EMBO J 1993;12:5131–5139.PubMedGoogle Scholar
  110. 110.
    Gardner DG, Newman ED, Nakamura KK, Nguyen KP. Endothelin increases the synthesis and secretion of atrial natriuretic peptide in neonatal rat cardiocytes. Am J Physiol 1991;261:E 177–182.Google Scholar
  111. 111.
    Shubeita HE, McDonough PM, Harris AN, Knowlton KU, Glembotski CC, Brown JH, Chien KR. Endothelin induction of inositol phospholipid hydrolysis, sarcomere assembly, and cardiac gene expression in ventricular myocytes. A paracrine mechanism for myocardial cell hypertrophy. J Biol Chem 1990;265:20,555–20,562.Google Scholar
  112. 112.
    Thibault G, Doubell AF, Garcia R, Lariviere R, Schiffrin EL. Endothelin-stimulated secretion of natriuretic peptides by rat atrial myocytes is mediated by endothelin A receptors. Circ Res 1994;74:460–470.PubMedGoogle Scholar
  113. 113.
    Irons CE, Murray SF, Glembotski CC. Identification of the receptor subtype responsible for endothe-lin-mediated protein kinase C activation and atrial natriuretic factor secretion from atrial myocytes. J Biol Chem 1993;268:23,417–23,421.Google Scholar
  114. 114.
    Sadoshima J, Izumo S. Molecular characterization of angiotensin II—induced hypertrophy of cardiac myocytes and hyperplasia of cardiac fibroblasts. Critical role of the ATI receptor subtype. Circ Res 1993;73:413–23.PubMedGoogle Scholar
  115. 115.
    Sadoshima J, Xu Y, Slayter HS, Izumo S. Autocrine release of angiotensin II mediates stretch-induced hypertrophy of cardiac myocytes in vitro. Cell 1993;75:977–984.PubMedCrossRefGoogle Scholar
  116. 116.
    Miyata S, Haneda T. Hypertrophic growth of cultured neonatal rat heart cells mediated by type 1 angiotensin II receptor. Am J Physiol 1994;266:H2443–2451.PubMedGoogle Scholar
  117. 117.
    Sadoshima J, Izumo S. Rapamycin selectively inhibits angiotensin II-induced increase in protein synthesis in cardiac myocytes in vitro. Potential role of 70–kD S6 kinase in angiotensin II-induced cardiac hypertrophy. Circ Res 1995;77:1040–1052.PubMedGoogle Scholar
  118. 118.
    Glembotski CC, Irons CE, Krown KA, Murray SF, Sprenkle AB, Sei CA. Myocardial alpha-thrombin receptor activation induces hypertrophy and increases atrial natriuretic factor gene expression. J Biol Chem 1993;268:20,646–20,652.Google Scholar
  119. 119.
    Parker TG, Chow KL, Schwartz RJ, Schneider MD. Differential regulation of skeletal alpha-actin transcription in cardiac muscle by two fibroblast growth factors. Proc Natl Acad Sei USA 1990;87:7066–7070.CrossRefGoogle Scholar
  120. 120.
    Tokola H, Salo K, Vuolteenaho O, Ruskoaho H. Basal and acidic fibroblast growth factor-induced atrial natriuretic peptide gene expression and secretion is inhibited by staurosporine. Eur J Pharmacol 1994;267:195–206.PubMedCrossRefGoogle Scholar
  121. 121.
    LaPointe MC, Deschepper CF, Wu JP, Gardner DG. Extracellular calcium regulates expression of the gene for atrial natriuretic factor. Hypertension 1990;15:20–28.PubMedGoogle Scholar
  122. 122.
    Irons CE, Sei CA, Hidaka H, Glembotski CC. Protein kinase C and calmodulin kinase are required for endothelin-stimulated atrial natriuretic factor secretion from primary atrial myocytes. J Biol Chem 1992;267:5211–5216.PubMedGoogle Scholar
  123. 123.
    Thorburn J, Frost JA, Thorburn A. Mitogen-activated protein kinases mediate changes in gene expression, but not cytoskeletal organization associated with cardiac muscle cell hypertrophy. J Cell Biol 1994;126:1565–1572.PubMedCrossRefGoogle Scholar
  124. 124.
    Sadoshima J, Izumo S. Mechanical stretch rapidly activates multiple signal transduction pathways in cardiac myocytes: potential involvement of an autocrine/paracrine mechanism. EMBO J 1993;12:1681–1692.PubMedGoogle Scholar
  125. 125.
    Gillespie-Brown J, Fuller SJ, Bogoyevitch MA, Cowley S, Sugden PH. The mitogen-activated protein kinase kinase MEK1 stimulates a pattern of gene expression typical of the hypertrophic phenotype in rat ventricular cardiomyocytes. J Biol Chem 1995;270:28,092–28,096.Google Scholar
  126. 126.
    Puceat M, Hilal-Dandan R, Strulovici B, Brunton LL, Brown JH. Differential regulation of protein kinase C isoforms in isolated neonatal and adult rat cardiomyocytes. J Biol Chem 1994;269:16,938–16,944.Google Scholar
  127. 127.
    Shields PP, Glembotski CC. Regulation of atrial natriuretic factor-(99–126) secretion from neonatal rat primary atrial cultures by activators of protein kinases A and C. J Biol Chem 1989;264:9322–9328.PubMedGoogle Scholar
  128. 128.
    LaPointe MC, Sitkins JR. Phorbol ester stimulates the synthesis and secretion of brain natriuretic peptide from neonatal rat ventricular cardiocytes: a comparison with the regulation of atrial natriuretic factor. Mol Endocrinol 1993;7:1284–1296.PubMedCrossRefGoogle Scholar
  129. 129.
    Kovacic-Milivojevic B, Gardner DG. Regulation of the human atrial natriuretic peptide gene in atrial cardiocytes by the transcription factor AP-1. Am J Hypertens 1993;6:258–263.PubMedGoogle Scholar
  130. 130.
    Shubeita HE, Martinson EA, Van Bilsen M, Chien KR, Brown JH. Transcriptional activation of the cardiac myosin light chain 2 and atrial natriuretic factor genes by protein kinase C in neonatal rat ventricular myocytes. Proc Natl Acad Sci USA 1992;89:1305–1309.PubMedCrossRefGoogle Scholar
  131. 131.
    LaMorte VJ, Thorburn J, Absher D, Spiegel A, Brown JH, Chien KR, Feramisco JR, Knowlton KU. Gq- and ras-dependent pathways mediate hypertrophy of neonatal rat ventricular myocytes following alpha 1–adrenergic stimulation. J Biol Chem 1994;269:13,490–13,496.Google Scholar
  132. 132.
    Thorburn A, Thorburn J, Chen SY, Powers S, Shubeita HE, Feramisco JR, Chien KR. HRas-dependent pathways can activate morphological and genetic markers of cardiac muscle cell hypertrophy [published erratum appears in J Biol Chem 1993 Jul 25;268(21):16,082]. J Biol Chem 1993;268:2244–2249.PubMedGoogle Scholar
  133. 133.
    Hunter JJ, Tanaka N, Rockman HA, Ross J, Chien KR. Ventricular expression of a MLC-2v-ras fusion gene induces cardiac hypertrophy and selective diastolic dysfunction in transgenic mice. J Biol Chem 1995;270:23,173–23,178.Google Scholar
  134. 134.
    Bogoyevitch MA, Glennon PE, Andersson MB, Clerk A, Lazou A, Marshall C J, Parker PJ, Sugden PH. Endothelin-1 and fibroblast growth factors stimulate the mitogen-activated protein kinase signaling cascade in cardiac myocytes. The potential role of the cascade in the integration of two signaling pathways leading to myocyte hypertrophy. J Biol Chem 1994;269:1110–1119.PubMedGoogle Scholar
  135. 135.
    Bogoyevitch MA, Clerk A, Sugden PH. Activation of the mitogen-activated protein kinase cascade by pertussis toxin-sensitive and -insensitive pathways in cultured ventricular cardiomyocytes. Biochem J 1995;309:437–443.PubMedGoogle Scholar
  136. 136.
    Post GR, Goldstein D, Thuerauf DJ, Glembotski CC, Brown JH. Dissociation of p44 and p42 mitogen-activated protein kinase activation from receptor-induced hypertrophy in neonatal rat ventricular myocytes. J Biol Chem 1996;271:8452–8457.PubMedCrossRefGoogle Scholar
  137. 137.
    Schiebinger RJ, Parr HG, Cragoe EJ Jr. Calcium: its role in alpha 1–adrenergic stimulation of atrial natriuretic peptide secretion. Endocrinology 1992;130:1017–1023.PubMedCrossRefGoogle Scholar
  138. 138.
    Schiebinger RJ. Calcium, its role in isoproterenol-stimulated atrial natriuretic peptide secretion by superfused rat atria. Circ Res 1989;65:600–606.PubMedGoogle Scholar
  139. 139.
    Okazaki T, Ando K, Igarashi T, Ogata E, Fujita T. Conserved mechanism of negative gene regulation by extracellular calcium. Parathyroid hormone gene versus atrial natriuretic polypeptide gene. J Clin Invest 1992;89:1268–1273.PubMedCrossRefGoogle Scholar
  140. 140.
    Greenwald JE, Apkon M, Hruska KA, Needleman P. Stretch-induced atriopeptin secretion in the isolated rat myocyte and its negative modulation by calcium. J Clin Invest 1989;83:1061–1065.PubMedCrossRefGoogle Scholar
  141. 141.
    De Bold ML, De Bold AJ. Effect of manipulation of Ca2+ environment on atrial natriuretic factor release. Am. J. Physiol. 1989;256:H1588–H1594.PubMedGoogle Scholar
  142. 142.
    Gardner DG, Schultz HD. Prostaglandins regulate the synthesis and secretion of the atrial natriuretic peptide. J Clin Invest 1990;86:52–59.PubMedCrossRefGoogle Scholar
  143. 143.
    Rayner TE, Chen BN, McLoughlin JW, Menadue MF, Norman RJ, Oliver JR. Prostaglandin F2 alpha mediates platelet-activating factor-stimulated atrial natriuretic factor release from the isolated rat heart. Endocrinology 1993;133:1108–1015.PubMedCrossRefGoogle Scholar
  144. 144.
    Kovacic-Milivojevic B, Schultz HD, Gardner DG. Arachidonic acid metabolites regulate the secretion of atrial natriuretic peptide in cultured rat atrial cardiocytes. Can J Physiol Pharmacol 1991;69:1493–1499.PubMedCrossRefGoogle Scholar
  145. 145.
    Pennica D, King KL, Shaw KJ, Luis E, Rullamas J, Luoh SM, Darbonne WC, Knutzon DS, Yen R, Chien KR, et al. Expression cloning of cardiotrophin 1, a cytokine that induces cardiac myocyte hypertrophy. Proc Natl Acad Sci USA 1995;92:1142–1146.PubMedCrossRefGoogle Scholar
  146. 146.
    Wollert KC, Taga T, Saito M, Narazaki M, Kishimoto T, Glembotski CC, Vernallis AN, Heath JK, Pennica D, Wood W.I, Chien KR. Cardiotrophin-1 activates a distinct form of cardiac muscle cell hypertrophy. J Biol Chem. 1996;271:9535–9545.PubMedCrossRefGoogle Scholar
  147. 147.
    Mukherjee DP, McTiernan CF, Sen S. Myotrophin induces early response genes and enhances cardiac gene expression. Hypertension 1993;21:142–148.PubMedGoogle Scholar
  148. 148.
    Yamamoto A, Kimura S, Hasui K, Fujisawa Y, Tamaki T, Fukui K, Iwao H, Abe Y. Calcitonin gene-related peptide (CGRP) stimulates the release of atrial natriuretic peptide (ANP) from isolated rat atria. Biochem Biophys Res Commun 1988;155:1452–1458.PubMedCrossRefGoogle Scholar
  149. 149.
    Schiebinger RJ, Santora AC. Stimulation by calcitonin gene-related peptide of atrial natriuretic peptide secretion in vitro and its mechanism of action. Endocrinology 1989;124:2473–2479.PubMedCrossRefGoogle Scholar
  150. 150.
    Schiebinger RJ, Cragoe EJ Jr. Ouabain. A stimulator of atrial natriuretic peptide secretion and its mechanism of action. Circ Res 1993;72:1035–1043.PubMedGoogle Scholar
  151. 151.
    Bloch KD, Zamir N, Lichtstein D, Seidman CE, Seidman JG. Ouabain induces secretion of proatrial natriuretic factor by rat atrial cardiocytes. Am J Physiol 1988;255:E383–387.PubMedGoogle Scholar
  152. 152.
    Sanchez-Ferrer CF, Burnett JC Jr, Lorenz RR, Vanhoutte PM. Possible modulation of release of atrial natriuretic factor by endothelium-derived relaxing factor. Am J Physiol 1990;259:H982–986.PubMedGoogle Scholar
  153. 153.
    Sadoshima J, Jahn L, Takahashi T, Kulik TJ, Izumo S. Molecular characterization of the stretch-induced adaptation of cultured cardiac cells. An in vitro model of load-induced cardiac hypertrophy. J Biol Chem 1992;267:10,551–10,560.Google Scholar
  154. 154.
    Gardner DG, Wirtz H, Dobbs LG. Stretch-dependent regulation of atrial peptide synthesis and secretion in cultured atrial cardiocytes. Am J Physiol 1992;263:E239–244.PubMedGoogle Scholar
  155. 155.
    Schiebinger RJ, Linden J. The influence of resting tension on immunoreactive atrial natriuretic peptide secretion by rat atria superfused in vitro. Circ Res 1986;59:105–109.PubMedGoogle Scholar
  156. 156.
    Dietz JR. Release of natriuretic factor from rat heart-lung preparation by atrial distension. Am J Physiol 1984;247:R1093–1096.PubMedGoogle Scholar
  157. 157.
    Rockman HA, Ross RS, Harris AN, Knowlton KU, Steinhelper ME, Field LJ, Ross J Jr, Chien KR. Segregation of atrial-specific and inducible expression of an atrial natriuretic factor transgene in an in vivo murine model of cardiac hypertrophy [published erratum appears in Proc Natl Acad Sci USA 1991 Nov 1;88(21):9907]. Proc Natl Acad Sci USA 1991;88:8277–8281.PubMedCrossRefGoogle Scholar
  158. 158.
    Ruskoaho H, Tholken H, Lang RE. Increase in atrial pressure releases atrial natriuretic peptide from isolated perfused rat hearts. Pflugers Arch 1986;407:170–174.PubMedCrossRefGoogle Scholar
  159. 159.
    Mangat H, de Bold AJ. Stretch-induced atrial natriuretic factor release utilizes a rapidly depleting pool of newly synthesized hormone. Endocrinology 1993;133:1398–1403.PubMedCrossRefGoogle Scholar
  160. 160.
    Schiebinger RJ, Greening KM. Interaction between stretch and hormonally stimulated atrial natriuretic peptide secretion. Am J Physiol 1992;262:H78–83.PubMedGoogle Scholar
  161. 161.
    Jiao JH, Baertschi AJ. Synergistic regulation of ANF in isolated rat hearts. Am J Physiol 1995;268:H1405–1411.PubMedGoogle Scholar
  162. 162.
    Mantymaa P, Vuolteenaho O, Marttila M, Ruskoaho H. Atrial stretch induces rapid increase in brain natriuretic peptide but not in atrial natriuretic peptide gene expression in vitro. Endocrinology 1993;133:1470–1473.PubMedCrossRefGoogle Scholar
  163. 163.
    Brown LA, Nunez DJ, Brookes CI, Wilkins MR. Selective increase in endothelin-1 and endothelin A receptor subtype in the hypertrophied myocardium of the aorto-venacaval fistula rat. Cardiovasc Res 1995;29:768–774.PubMedGoogle Scholar
  164. 164.
    Laine M, Arjamaa O, Vuolteenaho O, Ruskoaho H, Weckstrom M. Block of stretch-activated atrial natriuretic peptide secretion by gadolinium in isolated rat atrium. J Physiol (Lond) 1994;480:553–561.PubMedGoogle Scholar
  165. 165.
    Sadoshima J, Takahashi T, Jahn L, Izumo S. Roles of mechano-sensitive ion channels, cytoskeleton, and contractile activity in stretch-induced immediate-early gene expression and hypertrophy of cardiac myocytes. Proc Natl Acad Sci USA 1992;89:9905–9909.PubMedCrossRefGoogle Scholar
  166. 166.
    Bilder GE, Siegl PK, Schofield TL, Friedman PA. Chronotropic stimulation: a primary effector for release of atrial natriuretic factor. Circ Res 1989;64:799–805.PubMedGoogle Scholar
  167. 167.
    Schiebinger RJ, Linden J. Effect of atrial contraction frequency on atrial natriuretic peptide secretion. Am J Physiol 1986;251:H1095–1099.PubMedGoogle Scholar
  168. 168.
    Schiebinger RJ, Li Y, Cragoe EJ Jr. Calcium dependency of frequency-stimulated atrial natriuretic peptide secretion. Hypertension 1994;23:710–716.PubMedGoogle Scholar
  169. 169.
    McDonough PM, Glembotski CC. Induction of atrial natriuretic factor and myosin light chain-2 gene expression in cultured ventricular myocytes by electrical stimulation of contraction. J Biol Chem 1992;267:11,665–11,668.Google Scholar
  170. 170.
    McDonough PM, Stella SL, Glembotski CC. Involvement of cytoplasmic calcium and protein kinases in the regulation of atrial natriuretic factor secretion by contraction rate and endothelin. J Biol Chem 1994;269:9466–9472.PubMedGoogle Scholar
  171. 171.
    Lew RA, Baertschi AJ. Mechanisms of hypoxia-induced atrial natriuretic factor release from rat hearts. Am J Physiol 1989;257:H147–156.PubMedGoogle Scholar
  172. 172.
    Toth M, Vuorinen KH, Vuolteenaho O, Hassinen IE, Uusimaa PA, Leppaluoto J, Ruskoaho H. Hypoxia stimulates release of ANP and BNP from perfused rat ventricular myocardium. Am J Physiol 1994;266:H1572–1580.PubMedGoogle Scholar
  173. 173.
    Bloch KD, Scott JA, Zisfein JB, Fallon JT, Margolies MN, Seidman CE, Matsueda GR, Homey CJ, Graham RM, Seidman JG. Biosynthesis and secretion of proatrial natriuretic factor by cultured rat cardiocytes. Science 1985;230:1168–1171.PubMedCrossRefGoogle Scholar
  174. 174.
    Wildey GM, Fischman AJ, Fallon JT, Matsueda GR, Zisfein JB, Preibisch G, Seipke G, Homey CJ, Graham RM. Cellular processing of pro-atrial natriuretic factor (pro-ANF): studies using an antiserum that selectively binds ANF-(99–126) after its cleavage from pro-ANF. Endocrinology 1988;123:2054–2061.PubMedCrossRefGoogle Scholar
  175. 175.
    Vuolteenaho O, Arjamaa O, Ling N. Atrial natriuretic polypeptides (ANP): rat atria store high molecular weight precursor but secrete processed peptides of 25–35 amino acids. Biochem Biophys Res Commun 1985;129:82–88.PubMedCrossRefGoogle Scholar
  176. 176.
    Bloch KD, Seidman JG, Naftilan JD, Fallon JT, Seidman CE. Neonatal atria and ventricles secrete atrial natriuretic factor via tissue-specific secretory pathways. Cell 1986;47:695–702.PubMedCrossRefGoogle Scholar
  177. 177.
    Irons CE, Sei CA, Glembotski CC. Regulated secretion of atrial natriuretic factor from cultured ventricular myocytes. Am J Physiol 1993;264:H282–285.PubMedGoogle Scholar
  178. 178.
    Somlyo AV, Broderick R, Shuman H, Buhle EL Jr, Somlyo AP. Atrial-specific granules in situ have high calcium content, are acidic, and maintain anion gradients. Proc Natl Acad Sci USA 1988;85:6222–6226.PubMedCrossRefGoogle Scholar
  179. 179.
    Doubell AF, Bester AJ, Thibault G. Annexins V and VI: major calcium-dependent atrial secretory granule-binding proteins. Hypertension 1991;18:648–656.PubMedGoogle Scholar
  180. 180.
    Thibault G, Charbonneau C, Bilodeau J, Schiffrin EL, Garcia R. Rat brain natriuretic peptide is localized in atrial granules and released into the circulation. Am J Physiol 1992;263:R301–309.PubMedGoogle Scholar
  181. 181.
    Suzuki E, Hirata Y, Kohmoto O, Sugimoto T, Hayakawa H, Matsuoka H, Sugimoto T, Kojima M, Kangawa K, Minamino N, et al. Cellular mechanisms for synthesis and secretion of atrial natriuretic peptide and brain natriuretic peptide in cultured rat atrial cells. Circ Res 1992;71:1039–1048.PubMedGoogle Scholar
  182. 182.
    Ando K, Hirata Y, Emori T, Shichiri M, Kurosawa T, Sato K, Marumo F. Circulating forms of human atrial natriuretic peptide in patients with congestive heart failure. J Clin Endocrin Metab 1990;70:1603–1607.CrossRefGoogle Scholar
  183. 183.
    Ito T, Toki Y, Siegel N, Gierse JK, Needleman P. Manipulation of stretch-induced atriopeptin prohormone release and processing in the perfused rat heart. Proc Natl Acad Sci USA 1988;85:8365–8369.PubMedCrossRefGoogle Scholar
  184. 184.
    Greenwald JE, Needleman P, Siegel N, Tetens E, Biel B, Ritter D. Processing of atriopeptin prohormone by nonmyocytic atrial cells. Biochem Biophys Res Commun 1992;188:644–654.PubMedCrossRefGoogle Scholar
  185. 185.
    Dube GR, Kuroski-de Bold ML, de Bold AJ. Post-translational processing of atrial natriuretic factor by adult rat atrial cardiocytes in culture. Can J Physiol Pharmacol 1993;71:497–505.PubMedCrossRefGoogle Scholar
  186. 186.
    Corthorn J, Cantin M, Thibault G. Rat atrial secretory granules and pro-ANF processing enzyme. Mol Cell Biochem 1991;103:31–39.PubMedCrossRefGoogle Scholar
  187. 187.
    Sei CA, Hand GL, Murray SF, Glembotski CC. The cosecretional maturation of atrial natriuretic factor by primary atrial myocytes. Mol Endocrinol 1992;6:309–319.PubMedCrossRefGoogle Scholar
  188. 188.
    Shiono S, Nakao K, Morii N, Yamada T, Itoh H, Sakamoto M, Sugawara A, Saito Y, Katsuura G, Imura H. Nature of atrial natriuretic polypeptide in rat brain. Biochem Biophys Res Commun 1986; 135:728–734.PubMedCrossRefGoogle Scholar
  189. 189.
    Shields PP, Sprenkle AB, Taylor EW, Glembotski CC. Rat pro-atrial natriuretic factor expression and post-translational processing in mouse pituitary tumor cells. J Biol Chem 1990;265:10,905–10,911.Google Scholar
  190. 190.
    Gibson TR, Shields PP, Glembotski CC. The conversion of atrial natriuretic peptide (ANP)-(1–126) to ANP-(99–126) by rat serum: contribution to ANP cleavage in isolated perfused rat hearts. Endocrinology 1987;120:764–772.PubMedCrossRefGoogle Scholar
  191. 191.
    Bloch KD, Zisfein JB, Margolies MN, Homey CJ, Seidman JG, Graham RM. A serum protease cleaves proANF into a 14–kilodalton peptide and ANF. Am J Physiol 1987;252:E147–151.PubMedGoogle Scholar
  192. 192.
    Imada T, Takayanagi R, Inagami T. Atrioactivase, a specific peptidase in bovine atria for the processing of pro-atrial natriuretic factor. Purification and characterization. J Biol Chem 1988;263:9515–9519.PubMedGoogle Scholar
  193. 193.
    Wypij DM, Harris RB. Atrial granules contain an amino-terminal processing enzyme of atrial natriuretic factor. J Biol Chem 1988;263:7079–7086.PubMedGoogle Scholar
  194. 194.
    Rittenhouse J, Moberly L, Ahmed H, Marcus F. Phosphorylation in situ of atrial natriuretic peptide prohormone at the cyclic AMP-dependent site. J Biol Chem 1988;263:3778–3783.PubMedGoogle Scholar
  195. 195.
    Rittenhouse J, Moberly L, O’Donnell ME, Owen NE, Marcus F. Phosphorylation of atrial natriuretic peptides by cyclic AMP-dependent protein kinase. J Biol Chem 1986;261:7607–7610.PubMedGoogle Scholar
  196. 196.
    Bloch KD, Jones SW, Preibisch G, Seipke G, Seidman CE, Seidman JG. Proatrial natriuretic factor is phosphorylated by rat cardiocytes in culture. J Biol Chem 1987;262:9956–9961.PubMedGoogle Scholar
  197. 197.
    Wildey GM, Fischman AJ, Margolies MN, Graham RM, Homey CJ. Phosphorylation state of pro-atrial natriuretic factor in rat atrial secretory granules. Endocrinology 1990;127:2839–2848.PubMedCrossRefGoogle Scholar
  198. 198.
    Gagelmann M, Hock D, Forssmann WG. Relaxation of smooth muscle by cardiodilatin/atrial natriuretic peptide is inhibited by cAMP-dependent phosphorylation. FEBS Lett 1987;225:251–254.PubMedCrossRefGoogle Scholar
  199. 199.
    Olins GM, Mehta PP, Blehm DJ, Patton DR, Zupec ME, Whipple DE, Tjoeng FS, Adams SP, Olins PO, Gierse JK. Phosphorylation of high- and low-molecular-mass atrial natriuretic peptide analogs by cyclic AMP-dependent protein kinase. FEBS Lett 1987;224:325–330.PubMedCrossRefGoogle Scholar
  200. 200.
    Kubler D, Reinhardt D, Reed J, Pyerin W, Kinzel V. Atrial natriuretic peptide is phosphorylated by intact cells through cAMP-dependent ecto-protein kinase. Eur J Biochem 1992;206:179–186.PubMedCrossRefGoogle Scholar
  201. 201.
    Chien KR, Knowlton KU, Zhu H, Chien S. Regulation of cardiac gene expression during myocardial growth and hypertrophy: molecular studies of an adaptive physiologic response. FASEB J 1991;5:3037–3046.PubMedGoogle Scholar
  202. 202.
    Marban E, Koretsune Y. Cell calcium, oncogenes, and hypertrophy. Hypertension 1990; 15:652–658.PubMedGoogle Scholar
  203. 203.
    Schunkert H, Dzau VJ, Tang SS, Hirsch AT, Apstein CS, Lorell BH. Increased rat cardiac angiotensin converting enzyme activity and mRNA expression in pressure overload left ventricular hypertrophy. JClinlnves 1990;86:1913–1920.Google Scholar
  204. 204.
    Ito H, Hiroe M, Hirata Y, Fujisaki H, Adachi S, Akimoto H, Ohta Y, Marumo F. Endothelin ETA receptor antagonist blocks cardiac hypertrophy provoked by hemodynamic overload. Circulation 1994;89:2198–2203.PubMedGoogle Scholar
  205. 205.
    Arai M, Yoguchi A, Iso T, Takahashi T, Imai S, Murata K, Suzuki T. Endothelin-1 and its binding sites are upregulated in pressure overload cardiac hypertrophy. Am J Physiol 1995;268:H2084–2091.PubMedGoogle Scholar
  206. 206.
    Kovacic-Milivojevic B, Gardner DG. Divergent regulation of the human atrial natriuretic peptide gene by c-jun and c-fos. Mol Cell Biol 1992;12:292–301.PubMedGoogle Scholar
  207. 207.
    Bishopric NH, Jayasena V, Webster KA. Positive regulation of the skeletal alpha-actin gene by Fos and Jun in cardiac myocytes. J Biol Chem 1992;267:25,535–25,540.Google Scholar
  208. 208.
    Kovacic-Milivojevic B, Gardner DG. Fra-1, a Fos gene family member that activates atrial natriuretic peptide gene transcription. Hypertension 1995;25:679–682.PubMedGoogle Scholar
  209. 209.
    Kovacic-Milivojevic B, Wong VS, Gardner DG. Selective regulation of the atrial natriuretic peptide gene by individual components of the activator protein-1 complex. Endocrinology 1996; 137:1108–1117.PubMedCrossRefGoogle Scholar
  210. 210.
    Chiu R, Angel P, Karin M. Jun-B differs in its biological properties from, and is a negative regulator of, c-Jun. Cell 1989;59:979–986.PubMedCrossRefGoogle Scholar
  211. 211.
    Schutte J, Viallet J, Nau M, Segal S, Fedorko J, Minna J. jun-B inhibits and c-fos stimulates the transforming and trans-activating activities of c-jun. Cell 1989;59:987–997.PubMedCrossRefGoogle Scholar
  212. 212.
    Deng T, Karin M. JunB differs from c-Jun in its DNA-binding and dimerization domains, and represses c-Jun by formation of inactive heterodimers. Genes Dev 1993;7:479–490.PubMedCrossRefGoogle Scholar
  213. 213.
    Steinhelper ME, Cochrane KL, Field LJ. Hypotension in transgenic mice expressing atrial natriuretic factor fusion genes [see comments]. Hypertension 1990;16:301–307.PubMedGoogle Scholar
  214. 214.
    John SW, Krege JH, Oliver PM, Hagaman JR, Hodgin JB, Pang SC, Flynn TG, Smithies O. Genetic decreases in atrial natriuretic peptide and salt-sensitive hypertension. Science 1995;267:679–681.PubMedCrossRefGoogle Scholar
  215. 215.
    Lopez MJ, Wong SK, Kishimoto I, Dubois S, Mach V, Friesen J, Garbers DL, Beuve A. Salt-resistant hypertension in mice lacking the guanylyl cyclase-A receptor for atrial natriuretic peptide. Nature 1995;378:65–68.PubMedCrossRefGoogle Scholar

Copyright information

© Humana Press Inc. 1997

Authors and Affiliations

  • David G. Gardner
  • Jianming Wu
  • Branka Kovacic-Milivojevic

There are no affiliations available

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