| Beneficial hemodynamic, endocrine, and renal effects of urocortin in experimental heart failure: comparison with normal sheep. | |
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MedLine Citation:
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PMID: 12392842 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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OBJECTIVES: The goal of this study was to determine the bioactivity of urocortin (Ucn) in experimental heart failure (HF). BACKGROUND: Urocortin may participate in cardiovascular function and pressure/volume homeostasis. Its effects in HF are unknown. METHODS: Eight normal sheep and eight sheep with pacing-induced HF received ovine Ucn (10, 50, and 100 mg intravenous boluses at 2-h intervals) in vehicle-controlled studies. RESULTS: Urocortin boluses dose-dependently increased plasma Ucn (p < 0.001). Pharmacokinetics were similar in normal and HF sheep with half-lives approximating 1.3 and 19.5 h for the first and second phases, respectively. In HF, cardiac output increased (twofold), while peripheral resistance, left atrial pressure (both 50% falls: p < 0.001), and mean arterial pressure (p < 0.05) fell. In normal sheep, changes in peripheral resistance and atrial pressure were blunted and in arterial pressure were directionally opposite. Urocortin induced persistent, dose-dependent falls (30% to 50%) in plasma vasopressin, renin activity, aldosterone, natriuretic peptides (all p < 0.001), and endothelin-1 (p < 0.05) in HF sheep, while adrenocorticotrophic hormone and cortisol levels rose acutely (both p < 0.001). In comparison, Ucn in normal sheep resulted in a similar rise in cortisol and fall in aldosterone, no significant effects on plasma renin activity and natriuretic peptides, and a rise in vasopressin. Urocortin produced dose-dependent, sustained increases in urine volume (twofold, p < 0.01), sodium excretion (>9-fold rise, p < 0.001), and creatinine clearance (p < 0.001) in HF sheep. No significant renal effects were observed in normal sheep. CONCLUSIONS: Urocortin has profound and sustained hemodynamic, hormonal, and renal effects in experimental HF. Urocortin may have a role in pressure/volume homeostasis in HF and may provide a novel therapeutic approach to this disease. |
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Authors:
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Miriam T Rademaker; Christopher J Charles; Eric A Espiner; Steve Fisher; Christopher M Frampton; Carl M J Kirkpatrick; John G Lainchbury; M Gary Nicholls; A Mark Richards; Wylie W Vale |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Journal of the American College of Cardiology Volume: 40 ISSN: 0735-1097 ISO Abbreviation: J. Am. Coll. Cardiol. Publication Date: 2002 Oct |
Date Detail:
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Created Date: 2002-10-23 Completed Date: 2002-11-07 Revised Date: 2007-11-15 |
Medline Journal Info:
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Nlm Unique ID: 8301365 Medline TA: J Am Coll Cardiol Country: United States |
Other Details:
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Languages: eng Pagination: 1495-505 Citation Subset: AIM; IM |
Affiliation:
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Christchurch Cardioendocrine Research Group, Christchurch School of Medicine, Christchurch, New Zealand. miriam.rademaker@chmeds.ac.nz |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Blood Pressure / drug effects Cardiac Output / drug effects Corticotropin-Releasing Hormone / pharmacology* Dose-Response Relationship, Drug Heart Failure / physiopathology* Hemodynamics / drug effects*, physiology Homeostasis / physiology Kidney / drug effects, physiology Neuroprotective Agents / pharmacology* Renin-Angiotensin System / drug effects* Sheep Urocortins Vascular Resistance / drug effects |
| Chemical | |
Reg. No./Substance:
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0/Neuroprotective Agents; 0/Urocortins; 9015-71-8/Corticotropin-Releasing Hormone |
| Comments/Corrections | |
Erratum In:
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J Am Coll Cardiol. 2003 Aug 6;42(3):590 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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