Simko Fedor, Matuskova Jana, Luptak Ivan, Krajcirovicova Kristina, Kucharska Jarmila, Gvozdjakova Anna, Babal Pavel, Pechanova Olga
Department of Pathophysiology, School of Medicine, Comenius University, Sasinkova 4, 813 72, Bratislava, Slovak Republic.
Life Sci. 2004 Jan 23;74(10):1211-24. doi: 10.1016/j.lfs.2003.07.032.
3-Hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors have been shown to prevent or reverse hypertrophy of the LV in several models of left ventricular hypertrophy. The aim of the present study was to determine whether treatment with simvastatin can prevent hypertension, reduction of tissue nitric oxide synthase activity and left ventricular (LV) remodeling in NG-nitro-L-arginine methyl ester(L-NAME)-induced hypertension. Four groups of rats were investigated: control, simvastatin (10 mg/kg), L-NAME (40 mg/kg) and L-NAME + simvastatin (in corresponding doses). Animals were sacrificed and studied after 6 weeks of treatment. The decrease of NO-synthase activity in the LV, kidney and brain was associated with hypertension, LV hypertrophy and fibrosis development and remodeling of the aorta in the L-NAME group. Simvastatin attenuated the inhibition of NO-synthase activity in kidney and brain, partly prevented hypertension development and reduced the concentration of coenzyme Q in the LV. Nevertheless, myocardial hypertrophy, fibrosis and enhancement of DNA concentration in the LV, and remodeling of the aorta were not prevented by simultaneous simvastatin treatment in the L-NAME treated animals. We conclude that the HMG-CoA reductase inhibitor simvastatin improved nitric oxide production and partially prevented hypertension development, without preventing remodeling of the left ventricle and aorta in NO-deficient hypertension.
在几种左心室肥厚模型中，3-羟基-3-甲基戊二酰辅酶A（HMG-CoA）还原酶抑制剂已被证明可预防或逆转左心室肥厚。本研究的目的是确定辛伐他汀治疗是否能预防NG-硝基-L-精氨酸甲酯（L-NAME）诱导的高血压、组织一氧化氮合酶活性降低以及左心室（LV）重塑。研究了四组大鼠：对照组、辛伐他汀（10 mg/kg）组、L-NAME（40 mg/kg）组和L-NAME + 辛伐他汀（相应剂量）组。治疗6周后处死动物并进行研究。L-NAME组左心室、肾脏和大脑中一氧化氮合酶活性的降低与高血压、左心室肥厚、纤维化发展以及主动脉重塑有关。辛伐他汀减弱了肾脏和大脑中一氧化氮合酶活性的抑制，部分预防了高血压的发展，并降低了左心室中辅酶Q的浓度。然而，在L-NAME处理的动物中，同时使用辛伐他汀治疗并不能预防心肌肥厚、纤维化、左心室DNA浓度增加以及主动脉重塑。我们得出结论，HMG-CoA还原酶抑制剂辛伐他汀改善了一氧化氮的产生并部分预防了高血压的发展，但在一氧化氮缺乏的高血压中不能预防左心室和主动脉的重塑。
