Document Detail


Endogenous bradykinin suppresses myocardial fibrosis through the cardiac-generated endothelin system under chronic angiotensin-converting enzyme inhibition in heart failure.
MedLine Citation:
PMID:  15838317     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
In congestive heart failure, angiotensin-converting enzyme inhibitors (ACEIs) may prevent cardiac fibrosis via interaction with both angiotensin II and endothelin-1, which enhance myocardial collagen synthesis. However, whether endogenous bradykinin with an ACEI modifies the cardiac collagen architecture, affecting the endothelin system, has not yet been fully elucidated. We evaluated the changes in circulating hormonal factors, myocardial fibrosis and cardiac gene expression closely linked with heart failure, using an orally active specific bradykinin type 2 receptor antagonist, FR173657 (0.3 mg/kg/day, n = 6), with an ACEI, enalapril (1 mg/kg/day), in dogs with tachycardia-induced congestive heart failure (270 p.p.m., 22 days) and compared the effects with enalapril alone (n = 6). Although there were no differences observed in blood pressure, plasma renin activity, aldosterone and endothelin-1 levels, combined FR173657 significantly increased the cardiac expression of preproendothelin- 1 mRNA (P < 0.05) and collagen type I and type III mRNA (P < 0.05), and cardiac collagen deposits (P < 0.05), and decreased eNOS gene expression (P < 0.05) in the left ventricle compared with the ACEI-treated group. Furthermore, there was a significant negative correlation between the expression of preproendothelin- 1 and eNOS mRNA levels (r = -0.708, P < 0.001). In conclusion, bradykinin may prevent cardiac fibrosis in part via suppression of the local endothelin system in the failing heart through the enhancement of nitric oxide production under chronic angiotensin-converting enzyme inhibition.
Authors:
Masanori Fujii; Atsuyuki Wada; Masato Ohnishi; Takayoshi Tsutamoto; Takehiro Matsumoto; Takashi Yamamoto; Tomoyuki Takayama; Tomohiro Dohke; Takahiro Isono; Yutaka Eguchi; Minoru Horie
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of cardiovascular pharmacology     Volume:  44 Suppl 1     ISSN:  1533-4023     ISO Abbreviation:  J. Cardiovasc. Pharmacol.     Publication Date:  2004 Nov 
Date Detail:
Created Date:  2005-04-19     Completed Date:  2008-11-03     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  7902492     Medline TA:  J Cardiovasc Pharmacol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  S346-9     Citation Subset:  IM    
Affiliation:
Intensive Care Unit, Shiga University of Medical Science, Tsukinowa, Seta, Otsu, Japan.
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MeSH Terms
Descriptor/Qualifier:
Aldosterone / blood
Angiotensin-Converting Enzyme Inhibitors / pharmacology*
Animals
Bradykinin / metabolism*
Collagen / genetics,  metabolism*
Disease Models, Animal
Dogs
Enalapril / pharmacology*
Endothelin-1 / genetics,  metabolism*
Fibrosis
Heart Failure / drug therapy*,  metabolism,  pathology,  physiopathology
Hemodynamics / drug effects
Myocardium / enzymology,  metabolism*,  pathology
Nitric Oxide / metabolism
Nitric Oxide Synthase Type II / metabolism
Nitric Oxide Synthase Type III
Quinolines / pharmacology
RNA, Messenger / metabolism
Receptor, Bradykinin B2 / antagonists & inhibitors,  metabolism
Renin / blood
Chemical
Reg. No./Substance:
0/Angiotensin-Converting Enzyme Inhibitors; 0/Endothelin-1; 0/FR 173657; 0/Quinolines; 0/RNA, Messenger; 0/Receptor, Bradykinin B2; 10102-43-9/Nitric Oxide; 52-39-1/Aldosterone; 58-82-2/Bradykinin; 75847-73-3/Enalapril; 9007-34-5/Collagen; EC 1.14.13.39/Nitric Oxide Synthase Type II; EC 1.14.13.39/Nitric Oxide Synthase Type III; EC 1.14.13.39/Nos3 protein, rat; EC 3.4.23.15/Renin

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