Document Detail


Modification of left ventricular hypertrophy by chronic etomixir treatment.
MedLine Citation:
PMID:  10077244     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
1. Etomoxir (2[6(4-chlorophenoxy)hexyl]oxirane-2-carboxylate), an irreversible carnitine palmitoyl-transferase 1 inhibitor, reduces the expression of the myocardial foetal gene programme and the functional deterioration during heart adaption to a pressure-overload. Etomoxir may, however, also improve the depressed myocardial function of hypertrophied ventricles after a prolonged pressure overload. 2. To test this hypothesis, we administered racemic etomoxir (15 mg kg(-1) day(-1) for 6 weeks) to rats with ascending aortic constriction beginning 6 weeks after imposing the pressure overload. 3. The right ventricular/body weight ratio increased (P<0.05) by 20% in etomoxir treated rats (n = 10) versus untreated rats with ascending aortic constriction (n = 10). Left ventricular weight was increased (P<0.05) by 8%. Etomoxir blunted the increase in left ventricular chamber volume. Etomoxir raised the proportion of V1 isomyosin (35+/-4% versus 24+/-2%; P<0.05) and decreased the percentage of V3 isomyosin (36+/-4% versus 48+/-3%; P<0.05). 4. Maximum isovolumically developed pressure was higher in etomoxir treated rats than in untreated pressure overloaded rats (371+/-22 versus 315+/-23 mmHg; P<0.05). Maximum rates of ventricular pressure development (14,800+/-1310 versus 12,340+/-1030mmHg s(-1); P<0.05) and decline (6440+/-750 versus 5040+/-710 mmHg s(-1); P<0.05) were increased as well. Transformation of pressure values to ventricular wall stress data revealed an improved myocardial function which could partially account for the enhanced function of the whole left ventricle. 5. The co-ordinated action of etomoxir on ventricular mass, geometry and myocardial phenotype enhanced thus the pressure generating capacity of hypertrophied pressure-overloaded left ventricles and delayed the deleterious dilative remodelling.
Authors:
M Turcani; H Rupp
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  British journal of pharmacology     Volume:  126     ISSN:  0007-1188     ISO Abbreviation:  Br. J. Pharmacol.     Publication Date:  1999 Jan 
Date Detail:
Created Date:  1999-05-07     Completed Date:  1999-05-07     Revised Date:  2013-06-11    
Medline Journal Info:
Nlm Unique ID:  7502536     Medline TA:  Br J Pharmacol     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  501-7     Citation Subset:  IM    
Affiliation:
Institute of Physiology II, University of Tübingen, Germany.
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MeSH Terms
Descriptor/Qualifier:
Animals
Blood Pressure / drug effects
Body Weight / drug effects
Carnitine O-Palmitoyltransferase / antagonists & inhibitors
Enzyme Inhibitors / pharmacology*,  therapeutic use
Epoxy Compounds / pharmacology*,  therapeutic use
Heart Rate / drug effects
Heart Ventricles / drug effects,  enzymology,  physiopathology
Hypertrophy, Left Ventricular / drug therapy,  pathology,  physiopathology*
Isoenzymes / drug effects,  metabolism
Male
Myosins / drug effects,  metabolism
Organ Size / drug effects
Rats
Rats, Wistar
Ventricular Function, Left / drug effects,  physiology
Chemical
Reg. No./Substance:
0/Enzyme Inhibitors; 0/Epoxy Compounds; 0/Isoenzymes; EC 2.3.1.21/Carnitine O-Palmitoyltransferase; EC 3.6.4.1/Myosins; MSB3DD2XP6/etomoxir
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