Document Detail


Simvastatin decreased coenzyme Q in the left ventricle and skeletal muscle but not in the brain and liver in L-NAME-induced hypertension.
MedLine Citation:
PMID:  17824807     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase (statins) have been proven to reduce effectively cholesterol level and morbidity and mortality in patients with coronary heart disease and/or dyslipoproteinemia. Statins inhibit synthesis of mevalonate, a precursor of both cholesterol and coenzyme Q (CoQ). Inhibited biosynthesis of CoQ may be involved in some undesirable actions of statins. We investigated the effect of simvastatin on tissue CoQ concentrations in the rat model of NO-deficient hypertension induced by chronic L-NAME administration. Male Wistar rats were treated daily for 6 weeks with L-NAME (40 mg/kg) or with simvastatin (10 mg/kg), another group received simultaneously L-NAME and simvastatin in the same doses. Coenzyme Q(9) and Q(10) concentrations were analyzed by high performance liquid chromatography. L-NAME and simvastatin alone had no effect on CoQ concentrations. However, simultaneous application of L-NAME and simvastatin significantly decreased concentrations of both CoQ homologues in the left ventricle and slightly decreased CoQ(9) concentration in the skeletal muscle. No effect was observed on CoQ level in the liver and brain. We conclude that the administration of simvastatin under the condition of NO-deficiency reduced the level of CoQ in the heart and skeletal muscle what may participate in adverse effect of statins under certain clinical conditions.
Authors:
J Kucharská; A Gvozdjáková; F Simko
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2007-09-05
Journal Detail:
Title:  Physiological research / Academia Scientiarum Bohemoslovaca     Volume:  56 Suppl 2     ISSN:  0862-8408     ISO Abbreviation:  Physiol Res     Publication Date:  2007  
Date Detail:
Created Date:  2008-01-16     Completed Date:  2008-04-17     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9112413     Medline TA:  Physiol Res     Country:  Czech Republic    
Other Details:
Languages:  eng     Pagination:  S49-54     Citation Subset:  IM    
Affiliation:
School of Medicine, Comenius University, Bratislava, Slovak Republic. jarmila.kucharska@stonline.sk
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MeSH Terms
Descriptor/Qualifier:
Animals
Brain / drug effects*,  metabolism
Coenzymes / metabolism
Disease Models, Animal
Down-Regulation
Heart Ventricles / drug effects,  metabolism
Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacology*,  therapeutic use
Hypertension / chemically induced,  drug therapy*,  metabolism
Liver / drug effects*,  metabolism
Male
Muscle, Skeletal / drug effects*,  metabolism
NG-Nitroarginine Methyl Ester
Nitric Oxide / metabolism
Rats
Rats, Wistar
Simvastatin / pharmacology*,  therapeutic use
Time Factors
Ubiquinone / analogs & derivatives*,  metabolism
Chemical
Reg. No./Substance:
0/Coenzymes; 0/Hydroxymethylglutaryl-CoA Reductase Inhibitors; 10102-43-9/Nitric Oxide; 1339-63-5/Ubiquinone; 303-97-9/ubiquinone 9; 303-98-0/coenzyme Q10; 50903-99-6/NG-Nitroarginine Methyl Ester; 79902-63-9/Simvastatin

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


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