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在L-精氨酸甲酯(L-NAME)诱导的高血压中,辛伐他汀降低了左心室和骨骼肌中的辅酶Q,但未降低脑和肝脏中的辅酶Q。

Simvastatin decreased coenzyme Q in the left ventricle and skeletal muscle but not in the brain and liver in L-NAME-induced hypertension.

作者信息

Kucharská J, Gvozdjáková A, Simko F

机构信息

School of Medicine, Comenius University, Bratislava, Slovak Republic.

出版信息

Physiol Res. 2007;56 Suppl 2:S49-S54. doi: 10.33549/physiolres.931397. Epub 2007 Sep 5.

Abstract

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.

摘要

3-羟基-3-甲基戊二酰辅酶A(HMG-CoA)还原酶抑制剂(他汀类药物)已被证明能有效降低冠心病和/或血脂异常患者的胆固醇水平、发病率和死亡率。他汀类药物抑制甲羟戊酸的合成,甲羟戊酸是胆固醇和辅酶Q(CoQ)的前体。CoQ生物合成受抑制可能与他汀类药物的一些不良作用有关。我们研究了辛伐他汀对慢性给予L-硝基精氨酸甲酯(L-NAME)诱导的NO缺乏型高血压大鼠模型组织CoQ浓度的影响。雄性Wistar大鼠每天用L-NAME(40mg/kg)或辛伐他汀(10mg/kg)治疗6周,另一组同时给予相同剂量的L-NAME和辛伐他汀。通过高效液相色谱法分析辅酶Q9和Q10的浓度。单独使用L-NAME和辛伐他汀对CoQ浓度无影响。然而,同时应用L-NAME和辛伐他汀可显著降低左心室中两种CoQ同系物的浓度,并使骨骼肌中CoQ9浓度略有降低。未观察到对肝脏和脑中CoQ水平的影响。我们得出结论,在NO缺乏的情况下给予辛伐他汀会降低心脏和骨骼肌中的CoQ水平,这可能在某些临床条件下参与他汀类药物的不良反应。

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