Document Detail


Inhibitory effect of tranilast on hypertrophic collagen production in the spontaneously hypertensive rat heart.
MedLine Citation:
PMID:  9829619     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Tranilast, N-(3,4-dimethoxycinnamoyl) anthranilic acid, a widely used antiallergy drug in Japan, has been shown to inhibit transforming growth factor-beta1 release from fibroblasts and reduce collagen synthesis in keloid cells. In the present study, we have investigated the effect of this drug on cardiac hypertrophy in spontaneously hypertensive rats (SHR), with a focus on the cardiac collagen matrix, which is associated with myocardial stiffness. Twenty-four-week-old SHRs and Wistar Kyoto rats (WKYs) were administered tranilast (300 mg/kg) orally once a day for 4 weeks. This treatment significantly suppressed increases in left ventricular collagen concentration (P < 0.05) and the left ventricular weight/body weights ratios (P < 0.05) in SHRs, and tranilast was ineffective on collagen concentration and ventricular weight/body weights ratios in WKYs. Tranilast did not affect systolic or diastolic blood pressure, end-diastolic left ventricular pressure and heart rate in both SHRs and WKYs, and the agent did not change positive dp/dt or cardiac output in SHRs. The pressure-volume relationship curve was shifted to the left by the drug; the slope (k) of the logarithm of the pressure-volume relationship curve was significantly increased (P < 0.05) in SHRs. It is concluded that the suppression of increases in cardiac collagen and left ventricular mass by tranilast results in a corresponding prevention of cardiac stiffness as studied in the SHR.
Authors:
K Umemura; S Kikuchi; Y Suzuki; M Nakashima
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Japanese journal of pharmacology     Volume:  78     ISSN:  0021-5198     ISO Abbreviation:  Jpn. J. Pharmacol.     Publication Date:  1998 Oct 
Date Detail:
Created Date:  1999-01-14     Completed Date:  1999-01-14     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  2983305R     Medline TA:  Jpn J Pharmacol     Country:  JAPAN    
Other Details:
Languages:  eng     Pagination:  161-7     Citation Subset:  IM    
Affiliation:
Department of Pharmacology, Hamamatsu University School of Medicine, Japan.
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MeSH Terms
Descriptor/Qualifier:
Animals
Anthranilic Acids / pharmacology*
Anti-Allergic Agents / pharmacology*
Blood Pressure / drug effects
Body Weight / drug effects
Cardiac Output / drug effects
Cardiomegaly / metabolism*,  physiopathology
Collagen / biosynthesis,  drug effects*
Heart / drug effects,  physiology
Heart Rate / drug effects
Heart Ventricles / anatomy & histology,  drug effects,  physiopathology
Hemodynamics / drug effects
Hydroxyproline / drug effects,  metabolism
Male
Myocardium / metabolism
Organ Size / drug effects
Rats
Rats, Inbred SHR
Rats, Inbred WKY
Species Specificity
Ventricular Function, Left / drug effects
Chemical
Reg. No./Substance:
0/Anthranilic Acids; 0/Anti-Allergic Agents; 51-35-4/Hydroxyproline; 53902-12-8/tranilast; 9007-34-5/Collagen

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


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