Document Detail

Urocortin 2 combined with angiotensin-converting enzyme inhibition in experimental heart failure.
MedLine Citation:
PMID:  18052934     Owner:  NLM     Status:  MEDLINE    
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.
Miriam T Rademaker; Christopher J Charles; M Gary Nicholls; A Mark Richards
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Clinical science (London, England : 1979)     Volume:  114     ISSN:  1470-8736     ISO Abbreviation:  Clin. Sci.     Publication Date:  2008 May 
Date Detail:
Created Date:  2008-04-10     Completed Date:  2008-05-08     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7905731     Medline TA:  Clin Sci (Lond)     Country:  England    
Other Details:
Languages:  eng     Pagination:  635-42     Citation Subset:  IM    
Christchurch Cardioendocrine Research Group, Department of Medicine, Christchurch School of Medicine, Christchurch, New Zealand.
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MeSH Terms
Aldosterone / blood
Angiotensin-Converting Enzyme Inhibitors / therapeutic use*
Arginine Vasopressin / blood
Atrial Natriuretic Factor / blood
Blood Pressure / drug effects
Captopril / therapeutic use*
Cardiac Output / drug effects
Cardiac Pacing, Artificial
Drug Therapy, Combination
Endothelin-1 / blood
Epinephrine / blood
Heart Failure / blood,  drug therapy*
Models, Animal
Renin / blood
Renin-Angiotensin System / drug effects,  physiology
Urocortins / therapeutic use*
Vascular Resistance / drug effects
Reg. No./Substance:
0/Angiotensin-Converting Enzyme Inhibitors; 0/Endothelin-1; 0/Urocortins; 113-79-1/Arginine Vasopressin; 51-43-4/Epinephrine; 52-39-1/Aldosterone; 62571-86-2/Captopril; 85637-73-6/Atrial Natriuretic Factor; EC

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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