In heart failure, the cGMP to natriuretic peptide ratio is decreased and infusion of atrial natriuretic peptide (ANP) induces less cGMP generation. The ratio of the second messenger cGMP to plasma concentrations of ANP or brain natriuretic peptide (BNP) correlates with the effectiveness of natriuretic peptides. It was investigated whether blockade of the ETA receptor might improve the cGMP:NP ratio in heart failure. Patients with chronic heart failure (n = 142; mean age = 57 years) received oral treatment with the ETA antagonist darusentan (either 30, 100, 300mg/day or placebo) on top of standard therapy over a period of 21 days in a randomized, double-blind, placebo-controlled, multicentre study. Plasma concentrations of ANP, BNP and cGMP were determined before randomization and after 21 days of treatment. In parallel with decreased pulmonary and systemic vascular resistance, 3 weeks of oral treatment with the ETA receptor antagonist darusentan reduced BNP plasma levels and increased the cGMP:BNP ratio significantly. The improved cGMP:BNP ratio might reflect the ability of chronic ETA receptor blockade to facilitate the generation of the second messenger cGMP, which points towards a favourable modulation of the natriuretic peptide effector system, in addition to haemodynamic improvement in heart failure patients.
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September 2002
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Conference Article|
September 01 2002
Treatment with darusentan over 21 days improved cGMP generation in patients with chronic heart failure
Sebastian PHILIPP;
Sebastian PHILIPP
*Franz-Volhard-Klinik, Charite Campus Berlin-Buch, Helios Klinikum Berlin, Humboldt University, Wiltbergstrasse 50, 13125 Berlin, Germany
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Jan MONTI;
Jan MONTI
*Franz-Volhard-Klinik, Charite Campus Berlin-Buch, Helios Klinikum Berlin, Humboldt University, Wiltbergstrasse 50, 13125 Berlin, Germany
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Ines PAGEL;
Ines PAGEL
*Franz-Volhard-Klinik, Charite Campus Berlin-Buch, Helios Klinikum Berlin, Humboldt University, Wiltbergstrasse 50, 13125 Berlin, Germany
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Thomas LANGENICKEL;
Thomas LANGENICKEL
*Franz-Volhard-Klinik, Charite Campus Berlin-Buch, Helios Klinikum Berlin, Humboldt University, Wiltbergstrasse 50, 13125 Berlin, Germany
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Thomas NOTTER;
Thomas NOTTER
†Knoll-BASF Pharma, Ludwigshafen, Germany
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Frank RUSCHITZKA;
Frank RUSCHITZKA
‡Cardiovascular Center, University Hospital, Zurich, Switzerland
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Thomas LÜSCHER;
Thomas LÜSCHER
‡Cardiovascular Center, University Hospital, Zurich, Switzerland
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Rainer DIETZ;
Rainer DIETZ
*Franz-Volhard-Klinik, Charite Campus Berlin-Buch, Helios Klinikum Berlin, Humboldt University, Wiltbergstrasse 50, 13125 Berlin, Germany
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Roland WILLENBROCK
*Franz-Volhard-Klinik, Charite Campus Berlin-Buch, Helios Klinikum Berlin, Humboldt University, Wiltbergstrasse 50, 13125 Berlin, Germany
Dr R. Willenbrock (e-mail [email protected]).
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Publisher: Portland Press Ltd
Online ISSN: 1470-8736
Print ISSN: 0143-5221
© 2002 The Biochemical Society and the Medical Research Society
2002
Clin Sci (Lond) (2002) 103 (s2002): 249S–253S.
Citation
Sebastian PHILIPP, Jan MONTI, Ines PAGEL, Thomas LANGENICKEL, Thomas NOTTER, Frank RUSCHITZKA, Thomas LÜSCHER, Rainer DIETZ, Roland WILLENBROCK; Treatment with darusentan over 21 days improved cGMP generation in patients with chronic heart failure. Clin Sci (Lond) 1 September 2002; 103 (s2002): 249S–253S. doi: https://doi.org/10.1042/CS103S249S
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