| Endogenous urocortins reduce vascular tone and renin-aldosterone/endothelin activity in experimental heart failure. | |
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MedLine Citation:
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PMID: 15821006 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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AIMS: To investigate the role of the endogenous urocortin peptides in heart failure (HF) through blockade of the corticotropin-releasing factor receptor 2 (CRF-R2). METHODS AND RESULTS: Eight sheep were administered the CRF-R2 antagonist CRF(9-41) (1.5 mg bolus) before (Normal) and after development of pacing-induced HF. Compared with controls, CRF(9-41) in HF significantly increased mean arterial pressure (MAP) (71+/-2 vs. 75+/-2 mmHg, P=0.0024) and calculated total peripheral resistance (CTPR) (33.3+/-5.2 vs. 39.4+/-5.9 mmHg/L/min, P=0.0455). Similar trends were observed in the Normal state (MAP 87+/-1 vs. 89+/-2 mmHg, P=0.0689; CTPR 21.9+/-2.0 vs. 24.4+/-2.4 mmHg/L/min, P=0.0731). Left atrial pressure was elevated similarly in both states (Normal P=0.0013; HF P=0.0298), whereas cardiac output tended to be reduced (Normal P=0.0614). CRF(9-41) increased plasma urocortin-I (Normal 10.3+/-0.8 vs. 19.8+/-1.3 pmol/L, P<0.001; HF 14.4+/-0.9 vs. 25.3+/-0.8 pmol/L, P<0.001), renin (Normal 0.34+/-0.06 vs. 0.41+/-0.02 nmol/L/hr, P=0.013; HF 1.14+/-0.29 vs. 1.57+/-0.36 nmol/L/hr, P=0.0326), aldosterone (Normal 370+/-62 vs. 563+/-99 pmol/L, P=0.0813; HF 662+/-141 vs. 1024+/-209 pmol/L, P=0.095), and endothelin-1 (HF 3.18+/-0.18 vs. 4.74+/-1.04 pmol/L, P=0.0087). MAP, CTPR, renin, and endothelin-1 responses to CRF-R2 antagonism were significantly greater in HF than in the Normal state (P=0.049, 0.0427, 0.0311, and 0.0412, respectively). CONCLUSION: These data suggest that the endogenous urocortin peptides contribute to the suppression of vascular tone and renin-angiotensin-aldosterone/endothelin activation in HF and thus, play a protective compensatory role in this disorder. |
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Authors:
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Miriam T Rademaker; Chris J Charles; Eric A Espiner; Chris M Frampton; John G Lainchbury; A Mark Richards |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2005-04-08 |
Journal Detail:
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Title: European heart journal Volume: 26 ISSN: 0195-668X ISO Abbreviation: Eur. Heart J. Publication Date: 2005 Oct |
Date Detail:
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Created Date: 2005-09-19 Completed Date: 2006-03-14 Revised Date: 2007-11-15 |
Medline Journal Info:
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Nlm Unique ID: 8006263 Medline TA: Eur Heart J Country: England |
Other Details:
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Languages: eng Pagination: 2046-54 Citation Subset: IM |
Affiliation:
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Christchurch Cardioendocrine Research Group, Department of Medicine, The Christchurch School of Medicine, PO Box 4345, Christchurch, New Zealand. miriam.rademaker@chmeds.ac.nz |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Cardiac Output, Low / metabolism* Corticotropin-Releasing Hormone / physiology* Endothelins / physiology* Female Hemodynamics / physiology Random Allocation Receptors, Corticotropin-Releasing Hormone / antagonists & inhibitors* Renin-Angiotensin System / physiology* Sheep Urocortins |
| Chemical | |
Reg. No./Substance:
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0/CRF receptor type 2; 0/Endothelins; 0/Receptors, Corticotropin-Releasing Hormone; 0/Urocortins; 9015-71-8/Corticotropin-Releasing Hormone |
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