Document Detail


Efficient inhibition of the development of cardiac remodeling by a long-acting calcium antagonist amlodipine.
MedLine Citation:
PMID:  9449387     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The purpose of the present study was to examine the effects of a long-acting calcium antagonist, amlodipine, on the development of cardiac remodeling. Dihydropyridine calcium antagonists have been used widely for many years in the treatment of hypertension and angina pectoris. It has been reported, however, that a prototype of dihydropyridines, nifedipine, does not reduce mortality of patients with ischemic heart disease, possibly because of reflex stimulation of the sympathetic nervous system. A calcium antagonist, amlodipine, has been reported to have potential benefits by virtue of a gradual onset of action and a long duration of effects. Amlodipine (8 mg/kg per day, once a day) or nifedipine (24 mg/kg per day, three times a day) was administered to spontaneously hypertensive 12-week-old rats for 12 weeks. Left ventricular wall thickness was measured by echocardiography, and relative amounts of myosin heavy chain isoforms were assessed by pyrophosphate gels. Expressions of "fetal type" genes and type 1 collagen gene were examined by Northern blot analysis. Amlodipine and nifedipine both markedly reduced systolic blood pressure. However, the decrease in systolic blood pressure caused by nifedipine continued for no more than 8 hours, whereas the blood pressure-lowering effect of amlodipine continued for more than 16 hours post dose. Amlodipine markedly reduced left ventricular wall thickness, whereas nifedipine only weakly attenuated an increase in the wall thickness. Amlodipine, but not nifedipine, prevented an increase in the relative amount of V3 myosin heavy chain isoform and suppressed an increase in mRNA levels of beta-myosin heavy chain, skeletal alpha-actin, and type 1 collagen. Unlike nifedipine, amlodipine effectively prevented cardiac remodeling secondary to high blood pressure at biochemical levels and morphological levels. These results suggest that a long-acting calcium antagonist is more effective than a short-acting one in preventing organ injury in hypertensive subjects.
Authors:
T Yamazaki; I Komuro; Y Zou; S Kudoh; I Shiojima; T Mizuno; Y Hiroi; R Nagai; Y Yazaki
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Hypertension     Volume:  31     ISSN:  0194-911X     ISO Abbreviation:  Hypertension     Publication Date:  1998 Jan 
Date Detail:
Created Date:  1998-02-03     Completed Date:  1998-02-03     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  7906255     Medline TA:  Hypertension     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  32-8     Citation Subset:  IM    
Affiliation:
Department of Medicine III, University of Tokyo School of Medicine, the Health Service Center, Japan.
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MeSH Terms
Descriptor/Qualifier:
Amlodipine / pharmacology,  therapeutic use*
Animals
Antihypertensive Agents / pharmacology,  therapeutic use
Calcium Channel Blockers / pharmacology,  therapeutic use*
Cardiomegaly / etiology,  prevention & control*
Collagen / analysis,  drug effects
Heart / drug effects
Hypertension / complications,  drug therapy*
Male
Myocardium / chemistry
Myosin Heavy Chains / analysis,  drug effects
Nifedipine / pharmacology,  therapeutic use
Rats
Rats, Inbred SHR
Rats, Inbred WKY
Chemical
Reg. No./Substance:
0/Antihypertensive Agents; 0/Calcium Channel Blockers; 0/Myosin Heavy Chains; 21829-25-4/Nifedipine; 88150-42-9/Amlodipine; 9007-34-5/Collagen

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


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