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Horm Metab Res 2002; 34(2): 81-86
DOI: 10.1055/s-2002-20520
Original Clinical

© Georg Thieme Verlag Stuttgart · New York

Cessation of Pulmonary and Coronary Secretion of Adrenomedullin Peptides in the Progression of Human Heart Failure

K.  Stangl 1 , T.  Dschietzig 1 , C.  Richter 1 , V.  Stangl 1 , C.  Bartsch 1 , H.  R.  Zurbrügg 2 , R.  Pregla 2 , G.  Baumann 1 , S.  B.  Felix 1 , M.  Laule 1
  • 1 Medizinische Klinik m. S. Kardiologie, Angiologie, Pulmologie Charité (Campus Mitte), Humboldt-Universität zu Berlin, Germany
  • 2 German Heart Institute, Berlin, Germany
Further Information

Publication History

7 June 2001

8 November 2001

Publication Date:
04 March 2002 (online)

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Abstract

In human heart failure (CHF), adrenomedullin (AM) counteracts vasoconstriction and sodium retention. We investigated circulating levels of proadrenomedullin N-20 peptide (PAMP) and AM, and left ventricular expression of preproAM and calcitonin receptor-like receptor (CRLR) mRNA. Peptide levels were determined from the left ventricle, pulmonary artery, coronary sinus, and antecubital vein in patients demonstrating severe CHF (n = 12; mean ± SEM cardiac index, 1.9 ± 0.2 l/min/m2; pulmonary wedge pressure, 32 ± 1 mmHg), moderate CHF (n = 11; cardiac index, 2.9 ± 0.2; pulmonary wedge pressure, 14 ± 2), and in controls (n = 11). Left ventricular mRNA was quantified using RT-PCR and Southern blot hybridization. Depending on sites of measurement, PAMP and AM in severe CHF were 1.3 - 2.0 and 1.2 - 1.9 times as high as in moderate CHF, and 3.8 - 4.6 and 2.3 - 2.8 times as high as in controls. Only patients with moderate CHF demonstrated pulmonary and coronary net release of both peptides, that is, significant step-ups in concentrations between the pulmonary artery, left ventricle, and coronary sinus. In failing ventricles, preproAM mRNA increased 2.9 times above control, but CRLR mRNA was unchanged. Altogether, the heart and the lungs release AM peptides in moderate CHF. This secretion breaks down in severe CHF: a process that may contribute to and indicate decompensation. Unlike AM, the CRLR is not transcriptionally upregulated in severe CHF.

Key words

Hemodynamics - Catheterization - Radioimmunoassay - mRNA - Receptors

  • 1 Kitamura K, Kangawa K, Kawamoto M. Adrenomedullin: a novel hypotensive peptide isolated from human pheochromocytoma.  Biochem Biophys Res Commun. 1993;  192 553-560
    CrossrefPubMedGoogle Scholar
  • 2 Jougasaki M, Wei C M, Aarhus L L. Renal localization and actions of adrenomedullin: a natriuretic peptide.  Am J Physiol. 1995;  37 F657-F663
    PubMedGoogle Scholar
  • 3 Ginda W J, Nowak K W, Malendowicz L K. Decrease of TSH levels and epithelium/colloid ratio in rat thyroid glands following administration of proadrenomedullin N-terminal peptide (12-20).  Horm Metab Res. 2000;  32 10-14
    PubMedGoogle Scholar
  • 4 Hinson J P, Kapas S. The role of endothelial cell products in the regulation of adrenocortical function: actions of endothelin, nitric oxide, adrenomedullin and PAMP.  Horm Metab Res. 1998;  30 334-340
    Article in Thieme ConnectPubMedGoogle Scholar
  • 5 Yamaguchi T, Baba K, Doi Y, Yano K, Kitamura K, Eto T. Inhibition of aldosterone production by adrenomedullin, a hypotensive peptide, in the rat.  Hypertension. 1996;  28 308-314
    PubMedGoogle Scholar
  • 6 Samson W K. Adrenomedullin and the control of fluid and electrolyte homeostasis.  Annu Rev Physiol. 1999;  61 363-389
    CrossrefPubMedGoogle Scholar
  • 7 Yokoi H, Arima H, Murase T, Kondo K, Iwasaki Y, Oiso Y. Intracerebroventricular injection of adrenomedullin inhibits vasopressin release in conscious rats.  Neurosci Lett. 1996;  216 65-67
    CrossrefPubMedGoogle Scholar
  • 8 Jougasaki M, Wei C M, McKinley L J. Elevation of circulating and ventricular adrenomedullin in human congestive heart failure.  Circulation. 1995;  92 286-289
    PubMedGoogle Scholar
  • 9 Willenbrock R, Langenickel T, Knecht M. Regulation of cardiac adrenomedullin mRNA in different stages of experimental heart failure.  Life Sci. 1999;  65 2241-2249
    CrossrefPubMedGoogle Scholar
  • 10 Jougasaki M, Rodeheffer R J, Redfield M M. Cardiac secretion of adrenomedullin in human heart failure.  J Clin Invest. 1996;  97 2370-2376
    PubMedGoogle Scholar
  • 11 Nishikimi T, Horio T, Sasaki T. Cardiac production and secretion of adrenomedullin are increased in heart failure.  Hypertension. 1997;  30 1369-1375
    PubMedGoogle Scholar
  • 12 McLatchie L M, Fraser N J, Main M J. RAMPs regulate the transport and ligand specifity of the calcitonin receptor-like receptor.  Nature. 1998;  393 333-339
    CrossrefPubMedGoogle Scholar
  • 13 Shimosawa T, Ito Y, Ando K. Proadrenomedullin NH2-terminal 20 peptide, a new product of the adrenomedullin gene, inhibits norepinephrine overflow from nerve endings.  J Clin Invest. 1995;  96 1672-1676
    PubMedGoogle Scholar
  • 14 Etoh T, Kato J, Takenaga M. Differential hormonal profiles of adrenomedullin and proadrenomedullin N-terminal 20 peptide in patients with heart failure and effect of treatment on their plasma levels.  Clin Cardiol. 1999;  22 113-117
    PubMedGoogle Scholar
  • 15 Chomczynski P, Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction.  Anal Biochem. 1987;  162 156-159
    PubMedGoogle Scholar
  • 16 Bortz J, Lienert G A, Boehnke K. Verteilungsfreie Methoden in der Biostatistik, 3rd edition. Berlin; Springer Verlag 1990
    Google Scholar
  • 17 Holm S. A simple sequentially rejective multiple test procedure.  Scand J Stat. 1979;  6 65-70
    PubMedGoogle Scholar
  • 18 Nishikimi T, Matsuoka H, Shimada K. Production and clearance of two molecular forms of adrenomedullin in human plasma.  Am J Hypertens. 2000;  13 1032-1034
    CrossrefPubMedGoogle Scholar
  • 19 Hirayama N, Kitamura K, Imamura T. Secretion and clearance of the mature form of adrenomedullin in humans.  Life Sci. 1999;  64 2505-2509
    CrossrefPubMedGoogle Scholar
  • 20 Kakishita M, Nishikimi T, Okano Y. Increased plasma levels of adrenomedullin in patients with pulmonary hypertension.  Clin Sci. 1999;  96 33-39
    PubMedGoogle Scholar
  • 21 Trippodo N C, Cicila G T, Norman J A. Gene expression and enzyme activity of neutral endopeptidase 24.11 is not up-regulated in rats with congestive heart failure.  FASEB J. 1992;  6 A1490
    PubMedGoogle Scholar
  • 22 Abassi Z A, Kotob S, Golomb E. Pulmonary and renal neutral endopeptidase EC 3.4.24.11 in rats with experimental heart failure.  Hypertension. 1995;  25 1178-1184
    PubMedGoogle Scholar
  • 23 Kokkonen J O, Kuoppala A, Saarinen J. Kallidin- and bradykinin-degrading pathways in human heart. Degradation of kallidin by aminopeptidase M-like activity and bradykinin by neutral endopeptidase.  Circulation. 1999;  99 1984-1990
    PubMedGoogle Scholar
  • 24 Stangl K, Dschietzig T, Richter C. Pulmonary release and coronary and peripheral consumption of big endothelin and endothelin-1 in severe heart failure: Acute effects of vasodilator therapy.  Circulation. 2000;  102 1132-1138
    PubMedGoogle Scholar
  • 25 Nagaya N, Satoh T, Nishikimi T. Hemodynamic, renal, and hormonal effects of adrenomedullin infusion in patients with congestive heart failure.  Circulation. 2000;  101 498-503
    PubMedGoogle Scholar
  • 26 Oie E, Vinge L E, Yndestad A. Induction of a myocardial adrenomedullin signaling system during ischemic heart failure in rats.  Circulation. 2000;  101 415-422
    PubMedGoogle Scholar

Karl Stangl, M.D.

Medizinische Klinik und Poliklinik mit Schwerpunkt Kardiologie, Angiologie und Pulmologie · Charité (Campus Mitte), Humboldt-Universität zu Berlin

Schumannstraße 20/21 · 10098 Berlin · Germany

Phone: + 49 (30) 450-513 075/153

Fax: + 49 (30) 450-513 932

Email: karl.stangl@charite.de

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