Heart Failure Reviews

, 12:131 | Cite as

Natriuretic peptides and therapeutic applications

  • Candace Y. W. LeeEmail author
  • John C. BurnettJr.


Since the discovery of atrial natriuretic factor by de Bold et al., there has been tremendous progress in our understanding of the physiologic, diagnostic and therapeutic roles of the natriuretic peptides (NPs) in health and disease. Natriuretic peptides are endogenous hormones that are released by the heart in response to myocardial stretch and overload. Three mammalian NPs have been identified and characterized, including atrial natriuretic peptide (ANP or atrial natriuretic factor), B-type natriuretic peptide (BNP), and C-type natriuretic peptide (CNP). In addition, Dendroaspis natriuretic peptide (DNP) has been isolated from the venom of Dendroaspis angusticeps (the green mamba snake), and urodilatin from human urine. These peptides are structurally similar and they consist of a 17-amino-acid core ring and a cysteine bridge. Both ANP and BNP bind to natriuretic peptide receptor A (NPR-A) that are expressed in the heart and other organs. Activation of NPR-A generates an increase in cyclic guanosine monophosphate, which mediates natriuresis, inhibition of renin and aldosterone, as well as vasorelaxant, anti-fibrotic, anti-hypertrophic, and lusitropic effects. The NP system thus serves as an important compensatory mechanism against neurohumoral activation in heart failure. This provides a strong rationale for the use of exogenous NPs in the management of acutely decompensated heart failure. In this article, the therapeutic applications of NPs in the acute heart failure syndromes are reviewed. Emerging therapeutic agents and areas for future research are discussed.


Natriuretic peptides Heart Kidney cGMP Acute heart failure 



Supported by grants from the National Institutes of Health (HL36634; PO1 HL76611 and HL80732) and the Mayo Foundation. Dr. Lee is supported by the Clinical Research Initiative Fellowship from the Canadian Institutes of Health Research.


  1. 1.
    de Bold AJ, Borenstein HB, Veress AT, Sonnenberg H (1981) A rapid and potent natriuretic response to intravenous injection of atrial myocardial extract in rats. Life Sci 28:89–94PubMedGoogle Scholar
  2. 2.
    Boerrigter G, Burnett JC Jr (2004) Cardiorenal syndrome in decompensated heart failure: prognostic and therapeutic implications. Curr Heart Fail Rep 1:113–120PubMedGoogle Scholar
  3. 3.
    Chen HH, Burnett JC Jr (2006) Clinical application of the natriuretic peptides in heart failure. Eur Heart J 8(Suppl E):E18–E25Google Scholar
  4. 4.
    Potter LR, Abbey-Hosch S, Dickey DM (2006) Natriuretic peptides, their receptors, and cyclic guanosine monophosphate-dependent signaling functions. Endocr Rev 27:47–72PubMedGoogle Scholar
  5. 5.
    Schweitz H, Vigne P, Moinier D, Frelin C, Lazdunski M (1992) A new member of the natriuretic peptide family is present in the venom of the green mamba (Dendroaspis angusticeps). J Biol Chem 267:13928–13932PubMedGoogle Scholar
  6. 6.
    Schirger JA, Heublein DM, Chen HH, Lisy O, Jougasaki M, Wennberg PW et al (1999) Presence of Dendroaspis natriuretic peptide-like immunoreactivity in human plasma and its increase during human heart failure. Mayo Clin Proc 74:126–130PubMedGoogle Scholar
  7. 7.
    Margulies KB, Burnett JC Jr (2006) Visualizing the basis for paracrine natriuretic peptide signaling in human heart. Circ Res 99:113–115PubMedGoogle Scholar
  8. 8.
    Forssmann W, Meyer M, Forssmann K (2001) The renal urodilatin system: clinical implications. Cardiovasc Res 51:450–462PubMedGoogle Scholar
  9. 9.
    Burnett JC Jr, Costello-Boerrigter L, Boerrigter G (2004) Alterations in the kidney in heart failure: the cardiorenal axis in the regulation of sodium homeostasis. In: Mann DL (ed) Heart failure: a companion to Braunwald’s heart disease. Elsevier Inc, Philadelphia, pp 279–289Google Scholar
  10. 10.
    Suga S, Nakao K, Hosoda K, Mukoyama M, Ogawa Y, Shirakami G et al (1992) Receptor selectivity of natriuretic peptide family, atrial natriuretic peptide, brain natriuretic peptide, and C-type natriuretic peptide. Endocrinology 130:229–239PubMedGoogle Scholar
  11. 11.
    Singh G, Kuc RE, Maguire JJ, Fidock M, Davenport AP (2006) Novel snake venom ligand Dendroaspis natriuretic peptide is selective for natriuretic peptide receptor-A in human heart: downregulation of natriuretic peptide receptor-A in heart failure. Circ Res 99:183–190PubMedGoogle Scholar
  12. 12.
    Burnett JC Jr, Kao PC, Hu DC, Heser DW, Heublein D, Granger JP et al (1986) Atrial natriuretic peptide elevation in congestive heart failure in the human. Science 231:1145–1147PubMedGoogle Scholar
  13. 13.
    Mukoyama M, Nakao K, Hosoda K, Suga S, Saito Y, Ogawa Y et al (1991) Brain natriuretic peptide as a novel cardiac hormone in humans. Evidence for an exquisite dual natriuretic peptide system, atrial natriuretic peptide and brain natriuretic peptide. J Clin Invest 87:1402–1412PubMedGoogle Scholar
  14. 14.
    Sudoh T, Minamino N, Kangawa K, Matsuo H (1990) C-type natriuretic peptide (CNP): a new member of natriuretic peptide family identified in porcine brain. Biochem Biophys Res Commun 168:863–870PubMedGoogle Scholar
  15. 15.
    Stingo AJ, Clavell AL, Heublein DM, Wei CM, Pittelkow MR, Burnett JC Jr (1992) Presence of C-type natriuretic peptide in cultured human endothelial cells and plasma. Am J Physiol 263:H1318–1321PubMedGoogle Scholar
  16. 16.
    Del Ry S, Passino C, Emdin M, Giannessi D (2006) C-type natriuretic peptide and heart failure. Pharmacol Res 54:326–333 PubMedGoogle Scholar
  17. 17.
    Garbers DL, Chrisman TD, Wiegn P, Katafuchi T, Albanesi JP, Bielinski V et al (2006) Membrane guanylyl cyclase receptors: an update. Trends Endocrinol Metab 17:251–258PubMedGoogle Scholar
  18. 18.
    Ahluwalia A, MacAllister RJ, Hobbs AJ (2004) Vascular actions of natriuretic peptides. Cyclic GMP-dependent and -independent mechanisms. Basic Res Cardiol 99:83–89PubMedGoogle Scholar
  19. 19.
    Koller KJ, Lowe DG, Bennett GL, Minamino N, Kangawa K, Matsuo H et al (1991) Selective activation of the B natriuretic peptide receptor by C-type natriuretic peptide (CNP). Science 252:120–123PubMedGoogle Scholar
  20. 20.
    Wei CM, Aarhus LL, Miller VM, Burnett JC Jr (1993) Action of C-type natriuretic peptide in isolated canine arteries and veins. Am J Physiol 264:H71–H73PubMedGoogle Scholar
  21. 21.
    Wennberg PW, Miller VM, Rabelink T, Burnett JC Jr (1999) Further attenuation of endothelium-dependent relaxation imparted by natriuretic peptide receptor antagonism. Am J Physiol 277:H1618–H1621PubMedGoogle Scholar
  22. 22.
    Stingo AJ, Clavell AL, Aarhus LL, Burnett JC Jr (1992) Cardiovascular and renal actions of C-type natriuretic peptide. Am J Physiol 262:H308–H312PubMedGoogle Scholar
  23. 23.
    Furuya M, Yoshida M, Hayashi Y, Ohnuma N, Minamino N, Kangawa K et al (1991) C-type natriuretic peptide is a growth inhibitor of rat vascular smooth muscle cells. Biochem Biophys Res Commun 177:927–931PubMedGoogle Scholar
  24. 24.
    Cao L, Gardner DG (1995) Natriuretic peptides inhibit DNA synthesis in cardiac fibroblasts. Hypertension 25:227–234PubMedGoogle Scholar
  25. 25.
    Tokudome T, Horio T, Soeki T, Mori K, Kishimoto I, Suga S-i et al (2004) Inhibitory effect of C-type natriuretic peptide (CNP) on cultured cardiac myocyte hypertrophy: interference between CNP and endothelin-1 signaling pathways. Endocrinology 145:2131–2140PubMedGoogle Scholar
  26. 26.
    Igaki T, Itoh H, Suga SI, Hama N, Ogawa Y, Komatsu Y et al (1998) Effects of intravenously administered C-type natriuretic peptide in humans: comparison with atrial natriuretic peptide. Hypertens Res 21:7–13PubMedGoogle Scholar
  27. 27.
    Hunt PJ, Richards AM, Espiner EA, Nicholls MG, Yandle TG (1994) Bioactivity and metabolism of C-type natriuretic peptide in normal man. J Clin Endocrinol Metab 78:1428–1435PubMedGoogle Scholar
  28. 28.
    Hobbs A, Foster P, Prescott C, Scotland R, Ahluwalia A (2004) Natriuretic peptide receptor-C regulates coronary blood flow and prevents myocardial ischemia/reperfusion injury: novel cardioprotective role for endothelium-derived C-type natriuretic peptide. Circulation 110:1231–1235PubMedGoogle Scholar
  29. 29.
    Scotland RS, Cohen M, Foster P, Lovell M, Mathur A, Ahluwalia A et al (2005) C-type natriuretic peptide inhibits leukocyte recruitment and platelet-leukocyte interactions via suppression of P-selectin expression. Proc Natl Acad Sci USA 102:14452–14457PubMedGoogle Scholar
  30. 30.
    Soeki T, Kishimoto I, Okumura H, Tokudome T, Horio T, Mori K et al (2005) C-type natriuretic peptide, a novel antifibrotic and antihypertrophic agent, prevents cardiac remodeling after myocardial infarction. J Am Coll Cardiol 45:608–616PubMedGoogle Scholar
  31. 31.
    Nazario B, Hu RM, Pedram A, Prins B, Levin ER (1995) Atrial and brain natriuretic peptides stimulate the production and secretion of C-type natriuretic peptide from bovine aortic endothelial cells. J Clin Invest 95:1151–1157PubMedGoogle Scholar
  32. 32.
    Carstens J, Jensen KT, Pedersen EB (1998) Metabolism and action of urodilatin infusion in healthy volunteers. Clin Pharmacol Ther 64:73–86PubMedGoogle Scholar
  33. 33.
    Saxenhofer H, Fitzgibbon WR, Paul RV (1993) Urodilatin: binding properties and stimulation of cGMP generation in rat kidney cells. Am J Physiol 264:F267–273PubMedGoogle Scholar
  34. 34.
    Koike J, Nonoguchi H, Terada Y, Tomita K, Marumo F (1993) Effect of urodilatin on cGMP accumulation in the kidney. J Am Soc Nephrol 3:1705–1709PubMedGoogle Scholar
  35. 35.
    Goetz K, Drummer C, Zhu JL, Leadley R, Fiedler F, Gerzer R (1990) Evidence that urodilatin, rather than ANP, regulates renal sodium excretion. J Am Soc Nephrol 1:867–874PubMedGoogle Scholar
  36. 36.
    Gheorghiade M, Zannad F, Sopko G, Klein L, Pina IL, Konstam MA et al (2005) Acute heart failure syndromes: Current state and framework for future research. Circulation 112:3958–3968PubMedGoogle Scholar
  37. 37.
    Burnett JC (2005) Nesiritide: new hope for acute heart failure syndromes? Eur Heart J 7(Suppl B):B25–B30Google Scholar
  38. 38.
    Tan AC, Russel FG, Thien T, Benraad TJ (1993) Atrial natriuretic peptide. An overview of clinical pharmacology and pharmacokinetics. Clin Pharmacokinet 24:28–45PubMedGoogle Scholar
  39. 39.
    Nakao K, Sugawara A, Morii N, Sakamoto M, Yamada T, Itoh H et al (1986) The pharmacokinetics of alpha-human atrial natriuretic polypeptide in healthy subjects. Eur J Clin Pharmacol 31:101–103PubMedGoogle Scholar
  40. 40.
    Weidmann P, Hasler L, Gnadinger MP, Lang RE, Uehlinger DE, Shaw S et al (1986) Blood levels and renal effects of atrial natriuretic peptide in normal man. J Clin Invest 77:734–742PubMedGoogle Scholar
  41. 41.
    Eiskjaer H, Pedersen EB (1993) Dose-response study of atrial natriuretic peptide bolus injection in healthy man. Eur J Clin Invest 23:37–45PubMedGoogle Scholar
  42. 42.
    Cody RJ, Atlas SA, Laragh JH, Kubo SH, Covit AB, Ryman KS et al (1986) Atrial natriuretic factor in normal subjects and heart failure patients. Plasma levels and renal, hormonal, and hemodynamic responses to peptide infusion. J Clin Invest 78:1362–1374PubMedGoogle Scholar
  43. 43.
    Lindenfeld J, Schrier RW (2007) The kidney in heart failure. In: Hosenpud JD, Greenberg BH (eds) Congestive heart failure, 3rd edn.Lippincott Williams & Wilkins, Philadelphia, PA, pp 243–260Google Scholar
  44. 44.
    Hawkridge AM, Heublein DM, Bergen HR 3rd, Cataliotti A, Burnett JC Jr, Muddiman DC (2005) Quantitative mass spectral evidence for the absence of circulating brain natriuretic peptide (BNP-32) in severe human heart failure. Proc Natl Acad Sci USA 102:17442–17447PubMedGoogle Scholar
  45. 45.
    Giles TD, Quiroz AC, Roffidal LE, Marder H, Sander GE (1991) Prolonged hemodynamic benefits from a high-dose bolus injection of human atrial natriuretic factor in congestive heart failure. Clin Pharmacol Ther 50:557–563PubMedCrossRefGoogle Scholar
  46. 46.
    Suwa M, Seino Y, Nomachi Y, Matsuki S, Funahashi K (2005) Multicenter prospective investigation on efficacy and safety of carperitide for acute heart failure in the ‘real world’ of therapy. Circ J Mar 69(3):283–90Google Scholar
  47. 47.
    Keating GM, Goa KL (2003) Nesiritide: a review of its use in acute decompensated heart failure. Drugs 63:47–70PubMedGoogle Scholar
  48. 48.
    Sackner-Bernstein JD, Skopicki H, Aaronson KD (2006) Natriuretic peptides for the treatment of heart failure. In: Feldman A (ed) Heart failure: pharmacologic management. Blackwell Publishing, Malden, MA, pp 154–171Google Scholar
  49. 49.
    Heart Failure Society of America. HFSA (2006) Comprehensive heart failure practice guideline: Section 12: Evaluation and management of patients with acute decompensated heart failure. J Card Fail 12:e86–e103Google Scholar
  50. 50.
    Emdin M, Clerico A (2006) Cardiac natriuretic hormone system as target for cardiovascular therapy. In: Clerico A, Emdin M (eds) Natriuretic peptides: the hormones of the heart. Springer-Verlag, New York, pp 161–175Google Scholar
  51. 51.
    Colucci WS, Elkayam U, Horton DP, Abraham WT, Bourge RC, Johnson AD et al (2000) for the nesiritide study group. Intravenous nesiritide, a natriuretic peptide, in the treatment of decompensated congestive heart failure N Engl J Med 343:246–253PubMedGoogle Scholar
  52. 52.
    Publication Committee for the VMAC Investigators (Vasodilation in the Management of Acute CHF) (2002) Intravenous nesiritide vs nitroglycerin for treatment of decompensated congestive heart failure: a randomized controlled trial. JAMA 287:1531–1540 [Erratum, JAMA (2002) 1288:1577]Google Scholar
  53. 53.
    Hunt SA (2005) ACC/AHA 2005 guideline update for the diagnosis and management of chronic heart failure in the adult: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (writing committee to update the 2001 guidelines for the evaluation and management of heart failure). J Am Coll Cardiol 46:e1–e82PubMedGoogle Scholar
  54. 54.
    Nieminen MS, Bohm M, Cowie MR, Drexler H, Filippatos GS, Jondeau G et al (2005) Executive summary of the guidelines on the diagnosis and treatment of acute heart failure: the task force on acute heart failure of the European society of cardiology. Eur Heart J 26:384–416PubMedGoogle Scholar
  55. 55.
    Adams KF, Lindenfeld J, Arnold JMO, Baker DW, Barnard DH, Baughman KL et al HFSA (2006) Comprehensive Heart Failure Practice Guidelines. J Cardiac Failure 12:e1–e122Google Scholar
  56. 56.
    Dorner GT, Selenko N, Kral T, Schmetterer L, Eichler HG, Wolzt M (1998) Hemodynamic effects of continuous urodilatin infusion: a dose-finding study. Clin Pharmacol Ther 64:322–330PubMedGoogle Scholar
  57. 57.
    Bestle MH, Olsen NV, Christensen P, Jensen BV, Bie P (1999) Cardiovascular, endocrine, and renal effects of urodilatin in normal humans. Am J Physiol 276:R684–R695PubMedGoogle Scholar
  58. 58.
    Saxenhofer H, Raselli A, Weidmann P, Forssmann WG, Bub A, Ferrari P et al (1990) Urodilatin, a natriuretic factor from kidneys, can modify renal and cardiovascular function in men. Am J Physiol 259:F832–F838PubMedGoogle Scholar
  59. 59.
    Mitrovic V, Luss H, Nitsche K, Forssmann K, Maronde E, Fricke K et al (2005) Effects of the renal natriuretic peptide urodilatin (ularitide) in patients with decompensated chronic heart failure: a double-blind, placebo-controlled, ascending-dose trial. Am Heart J 150:1239PubMedGoogle Scholar
  60. 60.
    Cleland JGF, Coletta AP, Lammiman M, Witte KK, Loh H, Nasir M et al (2005) Clinical trials update from the European Society of Cardiology meeting 2005: CARE-HF extension study, ESSENTIAL, CIBIS-III, S-ICD, ISSUE-2, STRIDE-2, SOFA, IMAGINE, PREAMI, SIRIUS-II and ACTIVE. Eur J Heart Fail 7:1070–1075PubMedGoogle Scholar
  61. 61.
    Chen HH, Schirger JA, Alessandro C, Martin FL, Burnett JC (2006) Intra-renal infusion of BNP in experimental heart failure: A novel strategy to maximize the renal enhancing actions of BNP while minimizing arterial hypotension [abst]. J Card Fail 12:S32Google Scholar
  62. 62.
    Mathur VS, Goodson B, Patel S, Valencia A, Elkins J (2004) Evidence for substantial renal first pass effects of human b-type natriuretic peptide (nesiritide) following intra-renal infusion [abst]. J Card Fail 10:S68Google Scholar
  63. 63.
    Heywood JT, Ho A, Mathur V (2006) Favorable renal hemodynamic effects of intra-renal nesiritide infusion in heart transplant patients [abst]. J Card Fail 12:S3Google Scholar
  64. 64.
    Riter HG, Redfield MM, Burnett JC, Chen HH (2006) Nonhypotensive low-dose nesiritide has differential renal effects compared with standard-dose nesiritide in patients with acute decompensated heart failure and renal dysfunction [letter]. J Am Coll Cardiol 47:2334–2335PubMedGoogle Scholar
  65. 65.
    Luber JM Jr, The NAPA Investigators (2006) Perioperative nesiritide use is associated with decreased 180-day mortality in heart failure patients undergoing cardiothoracic surgery [abst]. J Card Fail 12:S73–S74Google Scholar
  66. 66.
    Oz MC. on behalf of the NAPA Investigators. Effect of perioperative nesiritide administration on postoperative renal function and clinical outcomes in patients undergoing cardiothoracic surgery: Results of the NAPA trial [abst]. Available at http://cicescardioorg/AbstractDetailsaspx?id = 28005 Accessed September 2, 2006Google Scholar
  67. 67.
    Zierer A, Safarzadeh E, Ewald GA, Pasque MK, Moon MR, Lawton JS et al (2006) Potential renal protective benefits of intra-operative BNP infusion during cardiac transplantation [abst]. Transplantation 82:564Google Scholar
  68. 68.
    Burnett JC Jr, Opgenorth TJ, Granger JP (1986) The renal action of atrial natriuretic peptide during control of glomerular filtration. Kidney Int 30:16–19PubMedGoogle Scholar
  69. 69.
    Brunner-La Rocca HP, Kaye DM, Woods RL, Hastings J, Esler MD (2001) Effects of intravenous brain natriuretic peptide on regional sympathetic activity in patients with chronic heart failure as compared with healthy control subjects. J Am Coll Cardiol 37:1221–1227PubMedGoogle Scholar
  70. 70.
    Bestle MH, Bie P (1993) Renal effects of urodilatin and atrial natriuretic peptide in volume expanded conscious dogs. Acta Physiol Scand 149:77–83PubMedCrossRefGoogle Scholar
  71. 71.
    Chen HH, Grantham JA, Schirger JA, Jougasaki M, Redfield MM, Burnett JC Jr (2000) Subcutaneous administration of brain natriuretic peptide in experimental heart failure. J Am Coll Cardiol 36:1706–1712PubMedGoogle Scholar
  72. 72.
    Chen HH, Lainchbury JG, Harty GJ, Burnett JC Jr (2002) Maximizing the natriuretic peptide system in experimental heart failure: subcutaneous brain natriuretic peptide and acute vasopeptidase inhibition. Circulation 105:999–1003PubMedGoogle Scholar
  73. 73.
    Chen HH, Schirger JA, Cataliotti A, Burnett JC Jr (2006) Intact acute cardiorenal and humoral responsiveness following chronic subcutaneous administration of the cardiac peptide BNP in experimental heart failure. Eur J Heart Fail published online Feb 2, 2006Google Scholar
  74. 74.
    Chen HH, Huntley BK, Schirger JA, Cataliotti A, Burnett JC Jr (2006) Maximizing the renal cyclic 3′-5′-guanosine monophosphate system with type V phosphodiesterase inhibition and exogenous natriuretic peptide: A novel strategy to improve renal function in experimental overt heart failure. J Am Soc Nephrol 17:2742–2747PubMedGoogle Scholar
  75. 75.
    Chen HH, Redfield MM, Nordstrom LJ, Horton DP, Burnett JC Jr (2004) Subcutaneous administration of the cardiac hormone BNP in symptomatic human heart failure. J Card Fail 10:115–119PubMedGoogle Scholar
  76. 76.
    Madhani M, Okorie M, Hobbs AJ, Macallister RJ (2006) Reciprocal regulation of human soluble and particulate guanylate cyclases in vivo. Br J Pharmacol published online October 3, 2006Google Scholar
  77. 77.
    Evgenov OV, Pacher P, Schmidt PM, Hasko G, Schmidt HH, Stasch JP (2006) NO-independent stimulators and activators of soluble guanylate cyclase: discovery and therapeutic potential. Nat Rev Drug Discov 5:755–768PubMedGoogle Scholar
  78. 78.
    Banga AK (2006) Oral delivery of peptide and protein drugs. Therapeutic peptides and proteins: formulation, processing, and delivery systems, 2nd edn. CRC Press, Boca Raton, FL, pp 229–258Google Scholar
  79. 79.
    Cataliotti A, Schirger JA, Martin FL, Chen HH, McKie PM, Boerrigter G et al (2005) Oral human brain natriuretic peptide activates cyclic guanosine 3′,5′-monophosphate and decreases mean arterial pressure. Circulation 112:836–840PubMedGoogle Scholar
  80. 80.
    Cataliotti A, Heublein DM, James KD, Burnett JC (2006) Biological actions of a novel oral human BNP in an experimental model of acute hypertension [abst]. J Card Fail 12:S30Google Scholar
  81. 81.
    Wang W, Ou Y, Shi Y (2004) AlbuBNP, a recombinant B-type natriuretic peptide and human serum albumin fusion hormone, as a long-term therapy of congestive heart failure. Pharm Res 21:2105–2111PubMedGoogle Scholar
  82. 82.
    Aaranson KD, Sackner-Bernstein JD (2006) Risk of death associated with nesiritide in patients with acutely decompensated heart failure. JAMA 296:1465–1466Google Scholar
  83. 83.
    Sackner-Bernstein JD, Kowalski M, Fox M, Aaronson K (2005) Short-term risk of death after treatment with nesiritide for decompensated heart failure: a pooled analysis of randomized controlled trials. JAMA 293:1900–1905PubMedGoogle Scholar
  84. 84.
    Sackner-Bernstein JD, Skopicki HA, Aaronson KD (2005) Risk of worsening renal function with nesiritide in patients with acutely decompensated heart failure. Circulation 111:1487–1491PubMedGoogle Scholar
  85. 85.
    Braunwald E, Burnett JC Jr, Colucci WS, et al. Natrecor Advisory Panel Report. In: Panel of cardiology experts provides recommendations to Scios regarding Natrecor. Healthcare Professional Letter. Fremont, CA: Scios June 13, 2005. Available at Accessed September 12, (2006)Google Scholar
  86. 86.
    Panel of cardiology experts provides recommendations to Scios regarding Natrecor. Healthcare Professional Letter. Fremont, CA: Scios June 13, 2005. Available at Accessed September 12, (2006)Google Scholar
  87. 87.
    Biollaz J, Nussberger J, Porchet M, Brunner-Ferber F, Otterbein ES, Gomez H et al (1986) Four-hour infusions of synthetic atrial natriuretic peptide in normal volunteers. Hypertension 8:II96–II105PubMedGoogle Scholar
  88. 88.
    Kentsch M, Drummer C, Gerzer R, Muller-Esch G (1995) Severe hypotension and bradycardia after continuous intravenous infusion of urodilatin (ANP 95-126) in a patient with congestive heart failure. Eur J Clin Invest 25:281–283PubMedGoogle Scholar
  89. 89.
    Burnett J, Boerrigter G (2005) cGMP enhancing strategies for acute and chronic heart failure [abst]. BMC Pharmacology 5:S22Google Scholar
  90. 90.
    Grantham JA, Borgeson DD, Burnett JC Jr (1997) BNP: pathophysiological and potential therapeutic roles in acute congestive heart failure. Am J Physiol 272:R1077–R1083PubMedGoogle Scholar
  91. 91.
    Best PJ, Burnett JC, Wilson SH, Holmes DR Jr, Lerman A (2002) Dendroaspis natriuretic peptide relaxes isolated human arteries and veins. Cardiovasc Res 55:375–384PubMedGoogle Scholar
  92. 92.
    Collins E, Bracamonte MP, Burnett JC Jr, Miller VM (2000) Mechanism of relaxations to dendroaspis natriuretic peptide in canine coronary arteries. J Cardiovasc Pharmacol 35:614–618PubMedGoogle Scholar
  93. 93.
    Singh G, Maguire JJ, Kuc RE, Skepper JN, Fidock M, Davenport AP (2006) Characterization of the snake venom ligand [125I]-DNP binding to natriuretic peptide receptor-A in human artery and potent DNP mediated vasodilatation. Br J Pharmacol published online October 16, 2006Google Scholar
  94. 94.
    Lainchbury JG, Lisy O, Burnett JC Jr, Meyer DM, Redfield MM (2002) Actions of a novel synthetic natriuretic peptide on hemodynamics and ventricular function in the dog. Am J Physiol Regul Integr Comp Physiol 282:R993–R998PubMedGoogle Scholar
  95. 95.
    Lisy O, Jougasaki M, Heublein DM, Schirger JA, Chen HH, Wennberg PW et al (1999) Renal actions of synthetic dendroaspis natriuretic peptide. Kidney Int 56:502–508PubMedGoogle Scholar
  96. 96.
    Lisy O, Lainchbury JG, Leskinen H, Burnett JC Jr (2001) Therapeutic actions of a new synthetic vasoactive and natriuretic peptide, dendroaspis natriuretic peptide, in experimental severe congestive heart failure. Hypertension 37:1089–1094PubMedGoogle Scholar
  97. 97.
    Chen HH, Lainchbury JG, Burnett JC Jr (2002) Natriuretic peptide receptors and neutral endopeptidase in mediating the renal actions of a new therapeutic synthetic natriuretic peptide dendroaspis natriuretic peptide. J Am Coll Cardiol 40:1186–1191PubMedGoogle Scholar
  98. 98.
    Lewis RJ, Garcia ML (2003) Therapeutic potential of venom peptides. Nat Rev Drug Discov 2:790–802PubMedGoogle Scholar
  99. 99.
    Fry BG (2005) From genome to “venome”: molecular origin and evolution of the snake venom proteome inferred from phylogenetic analysis of toxin sequences and related body proteins. Genome Res 15:403–420PubMedGoogle Scholar
  100. 100.
    Fry BG, Vidal N, Norman JA, Vonk FJ, Scheib H, Ramjan SF et al (2006) Early evolution of the venom system in lizards and snakes. Nature 439:584–588PubMedGoogle Scholar
  101. 101.
    Bazaa A, Marrakchi N, El Ayeb M, Sanz L, Calvete JJ (2005) Snake venomics: comparative analysis of the venom proteomes of the Tunisian snakes Cerastes cerastes, Cerastes vipera and Macrovipera lebetina. Proteomics 5:4223–4235PubMedGoogle Scholar
  102. 102.
    Barbouche R, Marrakchi N, Mansuelle P, Krifi M, Fenouillet E, Rochat H et al (1996) Novel anti-platelet aggregation polypeptides from Vipera lebetina venom: Isolation and characterization. FEBS Lett 392:6–10PubMedGoogle Scholar
  103. 103.
    Amininasab M, Elmi MM, Endlich N, Endlich K, Parekh N, Naderi-Manesh H et al (2004) Functional and structural characterization of a novel member of the natriuretic family of peptides from the venom of Pseudocerastes persicus. FEBS Lett 557:104–108PubMedGoogle Scholar
  104. 104.
    Michel GH, Murayama N, Sada T, Nozaki M, Saguchi K, Ohi H et al (2000) Two N-terminally truncated forms of C-type natriuretic peptide from habu snake venom. Peptides 21:609–615PubMedGoogle Scholar
  105. 105.
    Fry BG, Wickramaratana JC, Lemme S, Beuve A, Garbers D, Hodgson WC et al (2005) Novel natriuretic peptides from the venom of the inland taipan (Oxyuranus microlepidotus): isolation, chemical and biological characterisation. Biochem Biophys Res Commun 327:1011–1015PubMedGoogle Scholar
  106. 106.
    Ho PL, Soares MB, Maack T, Gimenez I, Puorto G, Furtado MF et al (1997) Cloning of an unusual natriuretic peptide from the South American coral snake Micrurus corallinus. Eur J Biochem 250:144–149PubMedGoogle Scholar
  107. 107.
    St Pierre L, Woods R, Earl S, Masci PP, Lavin MF (2005) Identification and analysis of venom gland-specific genes from the coastal taipan (Oxyuranus scutellatus) and related species. Cell Mol Life Sci 62:2679–2693PubMedGoogle Scholar
  108. 108.
    St Pierre L, Flight S, Masci PP, Hanchard KJ, Lewis RJ, Alewood PF et al (2006) Cloning and characterisation of natriuretic peptides from the venom glands of Australian elapids. Biochimie published online August 4, 2006Google Scholar
  109. 109.
    Murayama N, Hayashi MA, Ohi H, Ferreira LA, Hermann VV, Saito H et al (1997) Cloning and sequence analysis of a Bothrops jararaca cDNA encoding a precursor of seven bradykinin-potentiating peptides and a C-type natriuretic peptide. Proc Natl Acad Sci USA 94:1189–1193PubMedGoogle Scholar
  110. 110.
    Soares MR, Oliveira-Carvalho AL, Wermelinger LS, Zingali RB, Ho PL, Junqueira-de-Azevedo Ide L et al (2005) Identification of novel bradykinin-potentiating peptides and C-type natriuretic peptide from Lachesis muta venom. Toxicon 46:31–38PubMedGoogle Scholar
  111. 111.
    Ianzer D, Konno K, Marques-Porto R, Vieira Portaro FC, Stocklin R, Martins de Camargo AC et al (2004) Identification of five new bradykinin potentiating peptides (BPPs) from Bothrops jararaca crude venom by using electrospray ionization tandem mass spectrometry after a two-step liquid chromatography. Peptides 25:1085–1092PubMedGoogle Scholar
  112. 112.
    Hayashi MA, Camargo AC (2005) The Bradykinin-potentiating peptides from venom gland and brain of Bothrops jararaca contain highly site specific inhibitors of the somatic angiotensin-converting enzyme. Toxicon 45:1163–1170PubMedGoogle Scholar
  113. 113.
    Wei CM, Kim CH, Miller VM, Burnett JC Jr (1993) Vasonatrin peptide: a unique synthetic natriuretic and vasorelaxing peptide. J Clin Invest 92:2048–2052PubMedGoogle Scholar
  114. 114.
    Lisy O, Burnett JC Jr (2003) The design, synthesis and cardiorenal actions of a new chimeric natriuretic peptide CD-NP [abst]. J Am Coll Cardiol 41:312AGoogle Scholar
  115. 115.
    Lisy O, Burnett JC (2003) The new designer peptide CD-NP unloads the heart, suppresses renin and is natriuretic in vivo [abst]. J Card Fail 9:S32Google Scholar
  116. 116.
    Cataliotti A, Boerrigter G, Costello-Boerrigter LC, Schirger JA, Tsuruda T, Heublein DM et al (2004) Brain natriuretic peptide enhances renal actions of furosemide and suppresses furosemide-induced aldosterone activation in experimental heart failure. Circulation 109:1680–1685PubMedGoogle Scholar
  117. 117.
    Boerrigter G, Costello-Boerrigter LC, Lapp H, Stasch J-P, Burnett JC Jr (2005) Co-activation of soluble and particulate guanylate cyclase by BAY 58–2667 and BNP enhances cardiorenal function in experimental heart failure [abst]. J Card Fail 11(Suppl 1):S89Google Scholar
  118. 118.
    Costello-Boerrigter LC, Boerrigter G, Harty GJ, Burnett JC Jr (2006) Co-targeting of the V2 receptor with tolvaptan and the natriuretic peptide A-receptor with B-type natriuretic peptide enhances water and sodium excretion without adversely affecting renal function: A novel physiologic approach to sodium and water retention in experimental heart failure [abst]. J Card Fail 12:S84–S85Google Scholar
  119. 119.
    Hobbs AJ (2002) Soluble guanylate cyclase: An old therapeutic target re-visited. Br J Pharmacol 136:637–640PubMedGoogle Scholar
  120. 120.
    Friebe A, Koesling D (2003) Regulation of nitric oxide-sensitive guanylyl cyclase. Circ Res 93:96–105PubMedGoogle Scholar
  121. 121.
    Rothkegel C, Schmidt PM, Stoll F, Schroder H, Schmidt HH, Stasch JP (2006) Identification of residues crucially involved in soluble guanylate cyclase activation. FEBS Lett 580:4205–4213PubMedGoogle Scholar
  122. 122.
    Stasch JP, Schmidt P, Alonso-Alija C, Apeler H, Dembowsky K, Haerter M et al (2002) NO- and haem-independent activation of soluble guanylyl cyclase: molecular basis and cardiovascular implications of a new pharmacological principle. Br J Pharmacol 136:773–783PubMedGoogle Scholar
  123. 123.
    Ko FN, Wu CC, Kuo SC, Lee FY, Teng CM (1994) YC-1, a novel activator of platelet guanylate cyclase. Blood 84:4226–4233PubMedGoogle Scholar
  124. 124.
    Wu CC, Ko FN, Kuo SC, Lee FY, Teng CM (1995) YC-1 inhibited human platelet aggregation through NO-independent activation of soluble guanylate cyclase. Br J Pharmacol 116:1973–1978PubMedGoogle Scholar
  125. 125.
    Stasch JP, Becker EM, Alonso-Alija C, Apeler H, Dembowsky K, Feurer A et al (2001) NO-independent regulatory site on soluble guanylate cyclase. Nature 410:212–215PubMedGoogle Scholar
  126. 126.
    Boerrigter G, Costello-Boerrigter LC, Cataliotti A, Tsuruda T, Harty GJ, Lapp H et al (2003) Cardiorenal and humoral properties of a novel direct soluble guanylate cyclase stimulator BAY 41-2272 in experimental congestive heart failure. Circulation 107:686–689PubMedGoogle Scholar
  127. 127.
    Stasch J-P, Schmidt PM, Nedvetsky PI, Nedvetskaya TY, AK HS, Meurer S et al (2006) Targeting the heme-oxidized nitric oxide receptor for selective vasodilatation of diseased blood vessels. J Clin Invest 116:2552–2561PubMedCrossRefGoogle Scholar
  128. 128.
    Scios announces the ETNA clinical trial with nesiritide: ETNA trial to be largest study of acute heart failure ever conducted. Press release September 21, 2005. Available at Accessed September 29, 2006Google Scholar
  129. 129.
    Stiles S. Nesiritide shows hint of survival benefit in chronic-HF patients undergoing CABG. [HeartWire>Heart failure] September 12, 2006. Available at Accessed Sep 12, 2006Google Scholar
  130. 130.
    Baxter GF (2004) Natriuretic peptides and myocardial ischaemia. Basic Res Cardiol 99:90–93PubMedGoogle Scholar
  131. 131.
    Nieminen MS, Brutsaert D, Dickstein K, Drexler H, Follath F, Harjola V-P, et al (2006) EuroHeart Failure Survey II (EHFS II): a survey on hospitalized acute heart failure patients: description of population. Eur Heart J published online September 25, 2006:ehl193Google Scholar
  132. 132.
    Sezai A, Shiono M, Orime Y, Hata H, Hata M, Negishi N et al (2000) Low-dose continuous infusion of human atrial natriuretic peptide during and after cardiac surgery. Ann Thorac Surg 69:732–738PubMedGoogle Scholar
  133. 133.
    Wajima Z, Shiga T, Imanaga K, Inoue T, Ogawa R (2006) Effect of prophylactic bronchodilator treatment with i.v. carperitide on airway resistance and lung compliance after tracheal intubation. Br J Anaesth 96:660–664PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  1. 1.Cardiorenal Research Laboratory, Division of Cardiovascular Diseases, Departments of Internal Medicine and PhysiologyMayo Clinic College of MedicineRochesterUSA
  2. 2.Division of Clinical Pharmacology, Department of Molecular Pharmacology & Experimental TherapeuticsMayo Clinic College of MedicineRochesterUSA
  3. 3.Cardiorenal Research Laboratory, Guggenheim 915Mayo Clinic and FoundationRochesterUSA

Personalised recommendations