Ucn2 (urocortin 2) is a recently discovered peptide with therapeutic potential in heart failure. As any new treatment is likely to be used in conjunction with standard ACEI (angiotensin-converting enzyme inhibitor) therapy, it is important that the combined effects of these agents are assessed. In the present study, we investigated the effects of Ucn2 and an ACEI (captopril) administered for 3 h, both separately and together, in eight sheep with pacing-induced heart failure. Ucn2 and captopril alone both increased CO (cardiac output; Ucn2>captopril) and decreased arterial pressure (captopril>Ucn2), left atrial pressure (Ucn2>captopril) and peripheral resistance (Ucn2=captopril) relative to controls. Compared with either treatment alone, combined treatment further improved CO and reduced peripheral resistance and cardiac preload, without inducing further falls in blood pressure. In contrast with the marked increase in plasma renin activity observed with captopril alone, Ucn2 administration reduced renin activity, whereas the combined agents resulted in intermediate renin levels. All active treatments decreased circulating levels of aldosterone (Ucn2+captopril>Ucn2=captopril), endothelin-1 and the natriuretic peptides (Ucn2+captopril=Ucn2>captopril), whereas adrenaline (epinephrine) fell only with Ucn2 (Ucn2+captopril=Ucn2), and vasopressin increased during captopril alone. Ucn2, both separately and in conjunction with captopril, increased urine output, sodium and creatinine excretion and creatinine clearance. Conversely, captopril administered alone adversely affected these renal indices. In conclusion, co-treatment with Ucn2 and an ACEI in heart failure produced significantly greater improvements in haemodynamics, hormonal profile and renal function than achieved by captopril alone. These results indicate that dual treatment with these two agents is beneficial.
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May 2008
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Research Article|
April 14 2008
Urocortin 2 combined with angiotensin-converting enzyme inhibition in experimental heart failure
Miriam T. Rademaker;
1Christchurch Cardioendocrine Research Group, Department of Medicine, Christchurch School of Medicine, Christchurch, New Zealand
Correspondence: Dr Miriam T. Rademaker (email [email protected]).
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Christopher J. Charles;
Christopher J. Charles
1Christchurch Cardioendocrine Research Group, Department of Medicine, Christchurch School of Medicine, Christchurch, New Zealand
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M. Gary Nicholls;
M. Gary Nicholls
1Christchurch Cardioendocrine Research Group, Department of Medicine, Christchurch School of Medicine, Christchurch, New Zealand
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A. Mark Richards
A. Mark Richards
1Christchurch Cardioendocrine Research Group, Department of Medicine, Christchurch School of Medicine, Christchurch, New Zealand
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Publisher: Portland Press Ltd
Received:
October 15 2007
Revision Received:
November 26 2007
Accepted:
December 05 2007
Accepted Manuscript online:
December 05 2007
Online ISSN: 1470-8736
Print ISSN: 0143-5221
© The Authors Journal compilation © 2008 Biochemical Society
2008
Clin Sci (Lond) (2008) 114 (10): 635–642.
Article history
Received:
October 15 2007
Revision Received:
November 26 2007
Accepted:
December 05 2007
Accepted Manuscript online:
December 05 2007
Citation
Miriam T. Rademaker, Christopher J. Charles, M. Gary Nicholls, A. Mark Richards; Urocortin 2 combined with angiotensin-converting enzyme inhibition in experimental heart failure. Clin Sci (Lond) 1 May 2008; 114 (10): 635–642. doi: https://doi.org/10.1042/CS20070364
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