Document Detail

Ventricular production of natriuretic peptides and ventricular structural remodeling in hypertensive heart failure.
MedLine Citation:
PMID:  11593113     Owner:  NLM     Status:  MEDLINE    
OBJECTIVES: Brain natriuretic peptide (BNP) is a strong predictor of left ventricular (LV) hypertrophy (LVH) and dysfunction. However, our recent studies suggested that LVH is not necessarily associated with enhanced production of BNP in hypertension. This study aimed to clarify the relation of the characteristics of hypertrophy with the degree of gene expression of BNP in the developmental process of hypertensive heart failure. METHODS: Serial changes in LV geometry, histology and atrial natriuretic peptide (ANP) and BNP mRNA levels, were assessed in a hypertensive heart failure model using Dahl salt-sensitive rats (n = 24). We further studied effects of alpha1-receptor antagonist (doxazosin: 1 mg/kg per day, n = 5) and angiotensin II type 1 receptor (AT1R) antagonist (candesartan cilexetil: 1 mg/kg per day, n = 5). RESULTS: The BNP mRNA level was not elevated at the compensatory hypertrophic stage when ANP mRNA level was elevated. BNP mRNA level was increased with further progression of hypertrophy and development of fibrosis. AT1R blockade prevented such fibrosis and further progression of hypertrophy with normalization of BNP mRNA levels. Compensatory hypertrophy was not suppressed; therefore, ANP mRNA level, although decreased, was still beyond the normal level. The alpha1-receptor blockade slightly attenuated LV hypertrophy with a slight decrease in ANP mRNA levels. LV fibrosis was not prevented, and the BNP mRNA level was not decreased. CONCLUSIONS: BNP gene expression is not enhanced by initial compensatory hypertrophy, but is enhanced by LV fibrosis and late stage progression of hypertrophy dependent on AT1R-mediated signaling pathway.
Y Sakata; K Yamamoto; T Masuyama; T Mano; N Nishikawa; T Kuzuya; T Miwa; M Hori
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of hypertension     Volume:  19     ISSN:  0263-6352     ISO Abbreviation:  J. Hypertens.     Publication Date:  2001 Oct 
Date Detail:
Created Date:  2001-10-10     Completed Date:  2001-12-07     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  8306882     Medline TA:  J Hypertens     Country:  England    
Other Details:
Languages:  eng     Pagination:  1905-12     Citation Subset:  IM    
Department of Internal Medicine and Therapeutics, Osaka University Graduate School of Medicine, Suita, Japan.
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MeSH Terms
Atrial Natriuretic Factor / genetics
Cardiac Output, Low / etiology*,  pathology,  physiopathology*
Heart Ventricles
Hypertension / complications*
Myocardium / metabolism*,  pathology
Natriuretic Agents / biosynthesis*
Natriuretic Peptide, Brain / genetics
RNA, Messenger / metabolism
Rats, Inbred Dahl
Ventricular Remodeling*
Reg. No./Substance:
0/Natriuretic Agents; 0/RNA, Messenger; 114471-18-0/Natriuretic Peptide, Brain; 85637-73-6/Atrial Natriuretic Factor

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