Cessation of pulmonary and coronary secretion of adrenomedullin peptides in the progression of human heart failure.
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/m(2); 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.
Stangl
K
K
Medizinische Klinik m. S. Kardiologie, Angiologie, Pulmologie Charité (Campus Mitte), Humboldt-Universität zu Berlin, Germany. karl.stangl@charite.de
Dschietzig
T
T
Richter
C
C
Stangl
V
V
Bartsch
C
C
Zurbrügg
H R
HR
Pregla
R
R
Baumann
G
G
Felix
S B
SB
Laule
M
M
D053607:Adrenomedullin; D058286:Calcitonin Receptor-Like Protein; D005260:Female; D006333:Heart Failure / Q000188:drug therapy / Q000503:physiopathology*; D006352:Heart Ventricles / Q000737:chemistry; D006439:Hemodynamics; D006801:Humans; D008168:Lung / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000378:metabolism*; D009599:Nitroprusside / Q000627:therapeutic use; D010446:Peptide Fragments / Q000097:blood; D010455:Peptides / Q000097:blood / Q000378:metabolism*; D011498:Protein Precursors / Q000235:genetics; D011506:Proteins; D012333:RNA, Messenger / Q000032:analysis; D018003:Receptors, Calcitonin / Q000235:genetics; D014665:Vasodilator Agents / Q000627:therapeutic use
C545578:CALCRL protein, human; D058286:Calcitonin Receptor-Like Protein; D010446:Peptide Fragments; D010455:Peptides; D011498:Protein Precursors; D011506:Proteins; D012333:RNA, Messenger; D018003:Receptors, Calcitonin; D014665:Vasodilator Agents; C112034:preproadrenomedullin; D053607:Adrenomedullin; D009599:Nitroprusside