Advances in the treatment of heart failure may require manipulation of neurohumoral responses to cardiac impairment in addition to the established strategy of angiotensin-converting enzyme (ACE) inhibition. Importantly, since new treatments are likely to be used in conjunction with ACE inhibition therapy, the effects of the combination of agents need to be assessed. Adrenomedullin (ADM) is a peptide with potent vasodilator and natriuretic actions. ADM and an ACE inhibitor (captopril) were administered for 3h both separately and together in eight sheep with heart failure. Both ADM and captopril alone reduced arterial pressure, left atrial pressure (greater with captopril) and peripheral resistance, and increased cardiac output (greater with ADM). Compared with either treatment separately, combined ADM+captopril produced directionally similar but significantly greater changes in all haemodynamic variables (particularly falls in blood pressure). ADM increased renal sodium and creatinine excretion and creatinine clearance, and maintained urine output. Captopril and ADM+captopril reduced creatinine excretion and creatinine clearance, while urine volume and sodium excretion were not significantly altered. Plasma renin activity rose with all active treatments, whereas angiotensin II levels rose during ADM, but fell during captopril and ADM+captopril. Aldosterone was reduced by all active treatments. ADM+captopril reduced plasma noradrenaline (norepinephrine). In conclusion, short-term co-treatment with ADM and an ACE inhibitor produced significantly greater decreases in ventricular filling pressures and cardiac afterload, and increases in cardiac output, compared with either treatment alone. Despite the greater falls in blood pressure (and presumably renal perfusion pressure), renal function was maintained at a level similar to that observed with captopril alone.
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Research Article|
May 14 2002
Combined angiotensin-converting enzyme inhibition and adrenomedullin in an ovine model of heart failure
Miriam T. RADEMAKER;
*Christchurch Cardioendocrine Research Group, Department of Medicine, The Christchurch School of Medicine, P.O. Box 4345, Christchurch, New Zealand
Correspondence: Dr M.T. Rademaker (e-mail [email protected]).
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Chris J. CHARLES;
Chris J. CHARLES
*Christchurch Cardioendocrine Research Group, Department of Medicine, The Christchurch School of Medicine, P.O. Box 4345, Christchurch, New Zealand
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Garth J.S. COOPER;
Garth J.S. COOPER
†Developmental Biology and Cancer Research Group, School of Biological Sciences, University of Auckland, Private Bag 92019, Auckland, New Zealand
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David H. COY;
David H. COY
‡Department of Medicine, Tulane University, New Orleans, LA 70112, U.S.A.
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Eric A. ESPINER;
Eric A. ESPINER
*Christchurch Cardioendocrine Research Group, Department of Medicine, The Christchurch School of Medicine, P.O. Box 4345, Christchurch, New Zealand
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Lynley K. LEWIS;
Lynley K. LEWIS
*Christchurch Cardioendocrine Research Group, Department of Medicine, The Christchurch School of Medicine, P.O. Box 4345, Christchurch, New Zealand
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M. Gary NICHOLLS;
M. Gary NICHOLLS
*Christchurch Cardioendocrine Research Group, Department of Medicine, The Christchurch School of Medicine, P.O. Box 4345, Christchurch, New Zealand
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A. Mark RICHARDS
A. Mark RICHARDS
*Christchurch Cardioendocrine Research Group, Department of Medicine, The Christchurch School of Medicine, P.O. Box 4345, Christchurch, New Zealand
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Publisher: Portland Press Ltd
Accepted:
March 15 2001
Received:
August 20 2001
Revision Received:
November 28 2001
Online ISSN: 1470-8736
Print ISSN: 0143-5221
The Biochemical Society and the Medical Research Society © 2002
2002
Clin Sci (Lond) (2002) 102 (6): 653–660.
Article history
Accepted:
March 15 2001
Received:
August 20 2001
Revision Received:
November 28 2001
Citation
Miriam T. RADEMAKER, Chris J. CHARLES, Garth J.S. COOPER, David H. COY, Eric A. ESPINER, Lynley K. LEWIS, M. Gary NICHOLLS, A. Mark RICHARDS; Combined angiotensin-converting enzyme inhibition and adrenomedullin in an ovine model of heart failure. Clin Sci (Lond) 1 June 2002; 102 (6): 653–660. doi: https://doi.org/10.1042/cs1020653
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