Simvastatin decreased coenzyme Q in the left ventricle and skeletal muscle but not in the brain and liver in L-NAME-induced hypertension.
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.
Kucharská
J
J
School of Medicine, Comenius University, Bratislava, Slovak Republic. jarmila.kucharska@stonline.sk
Gvozdjáková
A
A
Simko
F
F
D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D003067:Coenzymes / Q000378:metabolism; D004195:Disease Models, Animal; D015536:Down-Regulation; D006352:Heart Ventricles / Q000187:drug effects / Q000378:metabolism; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D006973:Hypertension / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D019821:Simvastatin / Q000494:pharmacology* / Q000627:therapeutic use; D013997:Time Factors; D014451:Ubiquinone / Q000031:analogs & derivatives* / Q000378:metabolism