Document Detail


Cardiomyocyte apoptosis and cardiac angiotensin-converting enzyme in spontaneously hypertensive rats.
MedLine Citation:
PMID:  9369251     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Increased apoptosis has been reported in the heart of rats with spontaneous hypertension and cardiac hypertrophy. This study was designed to investigate the relationship between apoptosis and hypertrophy in cardiomyocytes from the left ventricle of spontaneously hypertensive rats (SHR). In addition, we evaluated whether the development of cardiomyocyte apoptosis is related to blood pressure or to the activity of the local angiotensin-converting enzyme (ACE) in SHR. The study was performed in 16-week-old SHR, 30-week-old untreated SHR, and 30-week-old SHR treated with quinapril (10 mg x kg[-1] x d[-1]) during 14 weeks before they were killed. Cardiomyocyte apoptosis was assessed by direct immunoperoxidase detection of digoxigenin-labeled 3'-hydroxyl ends of DNA. Nuclear polyploidization measured by DNA flow cytometry was used to assess cardiomyocyte hypertrophy. Compared with 16-week-old normotensive Wistar-Kyoto rats, 16-week-old SHR exhibited increased blood pressure (P<.001), increased rate of tetraploidy (P<.05), and similar levels of ACE activity and apoptosis. Compared with 30-week-old Wistar-Kyoto rats, 30-week-old SHR showed increased blood pressure (P<.001), increased ACE activity (P<.05), increased rate of tetraploidy (P<.01), and increased apoptosis (P<.01). Untreated 30-week-old SHR exhibited similar values of blood pressure and tetraploidy and higher ACE activity (P<.05) and apoptosis (P<.001) than 16-week-old SHR. A direct correlation (P<.01) was found between ACE activity and the apoptotic index in untreated 30-week-old SHR. The long-term administration of quinapril was associated with the normalization of ACE activity and apoptosis in treated SHR. These results suggest that the timing and mechanisms responsible for apoptosis and hypertrophy of cardiomyocytes are different in SHR. Whereas hypertrophy seems to be an earlier alteration that develops in parallel with hypertension, apoptosis develops later in association with overactivity of the local ACE. Our data suggest that cell death dysregulation may be a novel target for antihypertensive agents that interfere with the renin-angiotensin system in hypertension.
Authors:
J Díez; A Panizo; M Hernández; F Vega; I Sola; M A Fortuño; J Pardo
Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Hypertension     Volume:  30     ISSN:  0194-911X     ISO Abbreviation:  Hypertension     Publication Date:  1997 Nov 
Date Detail:
Created Date:  1997-12-10     Completed Date:  1997-12-10     Revised Date:  2003-11-14    
Medline Journal Info:
Nlm Unique ID:  7906255     Medline TA:  Hypertension     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  1029-34     Citation Subset:  IM    
Affiliation:
Vascular Pathophysiology Unit, School of Medicine, University of Navarra, Pamplona, Spain.
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MeSH Terms
Descriptor/Qualifier:
Animals
Apoptosis / physiology*
Blood Pressure
Fibrosis
Hypertension / metabolism*,  pathology*,  physiopathology
Hypertrophy, Left Ventricular / etiology
Myocardium / enzymology*,  pathology*
Peptidyl-Dipeptidase A / metabolism*
Rats
Rats, Inbred SHR / metabolism*
Rats, Inbred WKY
Chemical
Reg. No./Substance:
EC 3.4.15.1/Peptidyl-Dipeptidase A

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


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