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Haemodynamic, endocrine and renal actions of adrenomedullin 5 in an ovine model of heart failure

AM5 (adrenomedullin 5), a newly described member of the CGRP (calcitonin gene-related peptide) family, is reported to play a role in normal cardiovascular physiology. The effects of AM5 in HF (heart failure), however, have not been investigated. In the present study, we intravenously infused two inc...

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Autores principales: Rademaker, Miriam T., Charles, Christopher J., Nicholls, M. Gary, Richards, A. Mark
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Portland Press Ltd. 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3259696/
https://www.ncbi.nlm.nih.gov/pubmed/22087608
http://dx.doi.org/10.1042/CS20110483
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author Rademaker, Miriam T.
Charles, Christopher J.
Nicholls, M. Gary
Richards, A. Mark
author_facet Rademaker, Miriam T.
Charles, Christopher J.
Nicholls, M. Gary
Richards, A. Mark
author_sort Rademaker, Miriam T.
collection PubMed
description AM5 (adrenomedullin 5), a newly described member of the CGRP (calcitonin gene-related peptide) family, is reported to play a role in normal cardiovascular physiology. The effects of AM5 in HF (heart failure), however, have not been investigated. In the present study, we intravenously infused two incremental doses of AM5 (10 and 100 ng/min per kg of body weight each for 90 min) into eight sheep with pacing-induced HF. Compared with time-matched vehicle control infusions, AM5 produced progressive and dose-dependent increases in left ventricular dP/dt(max) [LD (low dose), +56 mmHg/s and HD (high dose), +152 mmHg/s] and cardiac output (+0.83 l/min and +1.81 l/min), together with decrements in calculated total peripheral resistance (−9.4 mmHg/min per litre and −14.7 mmHg/min per litre), mean arterial pressure (−2.8 mmHg and −8.4 mmHg) and LAP (left atrial pressure; −2.6 mmHg and −5.6 mmHg) (all P<0.001). HD AM5 significantly raised PRA (plasma renin activity) (3.5-fold increment, P<0.001), whereas plasma aldosterone levels were unchanged over the intra-infusion period and actually fell in the post-infusion period (70% decrement, P<0.01), resulting in a marked decrease in the aldosterone/PRA ratio (P<0.01). Despite falls in LAP, plasma atrial natriuretic peptide and B-type natriuretic peptide concentrations were maintained relative to controls. AM5 infusion also induced significant increases in urine volume (HD 2-fold increment, P<0.05) and urine sodium (2.7-fold increment, P<0.01), potassium (1.7-fold increment, P<0.05) and creatinine (1.4-fold increment, P<0.05) excretion and creatinine clearance (60% increment, P<0.05). In conclusion, AM5 has significant haemodynamic, endocrine and renal actions in experimental HF likely to be protective and compensatory in this setting. These results suggest that AM5 may have potential as a therapeutic agent in human HF.
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spelling pubmed-32596962012-01-18 Haemodynamic, endocrine and renal actions of adrenomedullin 5 in an ovine model of heart failure Rademaker, Miriam T. Charles, Christopher J. Nicholls, M. Gary Richards, A. Mark Clin Sci (Lond) Research Article AM5 (adrenomedullin 5), a newly described member of the CGRP (calcitonin gene-related peptide) family, is reported to play a role in normal cardiovascular physiology. The effects of AM5 in HF (heart failure), however, have not been investigated. In the present study, we intravenously infused two incremental doses of AM5 (10 and 100 ng/min per kg of body weight each for 90 min) into eight sheep with pacing-induced HF. Compared with time-matched vehicle control infusions, AM5 produced progressive and dose-dependent increases in left ventricular dP/dt(max) [LD (low dose), +56 mmHg/s and HD (high dose), +152 mmHg/s] and cardiac output (+0.83 l/min and +1.81 l/min), together with decrements in calculated total peripheral resistance (−9.4 mmHg/min per litre and −14.7 mmHg/min per litre), mean arterial pressure (−2.8 mmHg and −8.4 mmHg) and LAP (left atrial pressure; −2.6 mmHg and −5.6 mmHg) (all P<0.001). HD AM5 significantly raised PRA (plasma renin activity) (3.5-fold increment, P<0.001), whereas plasma aldosterone levels were unchanged over the intra-infusion period and actually fell in the post-infusion period (70% decrement, P<0.01), resulting in a marked decrease in the aldosterone/PRA ratio (P<0.01). Despite falls in LAP, plasma atrial natriuretic peptide and B-type natriuretic peptide concentrations were maintained relative to controls. AM5 infusion also induced significant increases in urine volume (HD 2-fold increment, P<0.05) and urine sodium (2.7-fold increment, P<0.01), potassium (1.7-fold increment, P<0.05) and creatinine (1.4-fold increment, P<0.05) excretion and creatinine clearance (60% increment, P<0.05). In conclusion, AM5 has significant haemodynamic, endocrine and renal actions in experimental HF likely to be protective and compensatory in this setting. These results suggest that AM5 may have potential as a therapeutic agent in human HF. Portland Press Ltd. 2012-01-16 2012-05-01 /pmc/articles/PMC3259696/ /pubmed/22087608 http://dx.doi.org/10.1042/CS20110483 Text en © 2012 The Author(s) The author(s) has paid for this article to be freely available under the terms of the Creative Commons Attribution Non-Commercial Licence (http://creativecommons.org/licenses/by-nc/2.5/) which permits unrestricted non-commercial use, distribution and reproduction in any medium, provided the original work is properly cited. http://creativecommons.org/licenses/by-nc/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Rademaker, Miriam T.
Charles, Christopher J.
Nicholls, M. Gary
Richards, A. Mark
Haemodynamic, endocrine and renal actions of adrenomedullin 5 in an ovine model of heart failure
title Haemodynamic, endocrine and renal actions of adrenomedullin 5 in an ovine model of heart failure
title_full Haemodynamic, endocrine and renal actions of adrenomedullin 5 in an ovine model of heart failure
title_fullStr Haemodynamic, endocrine and renal actions of adrenomedullin 5 in an ovine model of heart failure
title_full_unstemmed Haemodynamic, endocrine and renal actions of adrenomedullin 5 in an ovine model of heart failure
title_short Haemodynamic, endocrine and renal actions of adrenomedullin 5 in an ovine model of heart failure
title_sort haemodynamic, endocrine and renal actions of adrenomedullin 5 in an ovine model of heart failure
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3259696/
https://www.ncbi.nlm.nih.gov/pubmed/22087608
http://dx.doi.org/10.1042/CS20110483
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