Atorvastatin upregulates nitric oxide synthases with Rho-kinase inhibition and Akt activation in the kidney of spontaneously hypertensive rats
Atorvastatin upregulates nitric oxide synthases with Rho-kinase inhibition and Akt activation in the kidney of spontaneously hypertensive rats
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DOI：
10.1097/hjh.0b013e32833e0924
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发表时间：
2010-11-01
影响因子：
4.9
通讯作者：
Kohzuki, Masahiro
中科院分区：
文献类型：
--
作者：
Ito, Daisuke;Ito, Osamu;Kohzuki, Masahiro
目的3-羟基-3-甲基戊二酰辅酶A还原酶抑制剂他汀类药物具有降血压和治疗心血管、肾脏疾病的作用。观察阿托伐他汀(ATV)对自发性高血压大鼠(SHR)肾脏一氧化氮合酶(NOS)表达及Rho-K、Akt活性的影响。免疫印迹法检测肾组织内皮细胞、神经细胞和诱导型一氧化氮合酶(eNOS、nNOS和iNOS)蛋白的表达。通过测定eNOS、ezrin/Radixin/moesin(ERM)和Akt的磷酸化程度来检测肾脏eNOS、Rho-Kinase和Akt的活性。ATV可增加皮质和延髓eNOS的表达，增加延髓nNOS的表达，但不影响iNOS的表达。虽然ATV上调了肾脏eNOS的表达，但降低了皮质中磷酸化eNOS的水平，但不影响髓质中磷酸化eNOS与总eNOS的比率。ATV对SHR肾脏的Rho-Kinase活性有抑制作用，对Akt活性有上调作用。结论ATV通过抑制Rho-Kinase活性和Akt活性上调SHR肾脏eNOS和nNOS的表达。肾脏一氧化氮系统、Rho-Kinase和Akt可能参与他汀类药物的降压和肾脏保护作用。J Hyperten 28：2278-2288(C)2010 Wolters Kluwer Health|Lippincott Williams&Wilkins.
Objective 3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, statins reduce blood pressure and have beneficial effects in cardiovascular and kidney diseases. The present study examined the effect of chronic treatment with atorvastatin (ATV) on the expression of nitric oxide synthase (NOS) and the activity of Rho-kinase and Akt in the kidney of spontaneously hypertensive rats (SHRs).Methods SHRs were treated with ATV for 8 weeks and the SBP was measured. The expressions of endothelial, neuronal and inducible NOS (eNOS, nNOS and iNOS, respectively) proteins in the kidney were examined by immunoblot analysis. The activity of eNOS, Rho-kinase and Akt in the kidney was examined by assessing the phosphorylation of eNOS, ezrin/radixin/moesin (ERM) and Akt, respectively.Results ATV reduced the SBP without changing the plasma cholesterol levels. ATV increased eNOS expression in the cortex and medulla and nNOS expression in the medulla, whereas it did not affect iNOS expression. Although it upregulated eNOS expression in the kidney, ATV decreased the levels of phosphorylated eNOS in the cortex and did not affect the ratio of phosphorylated eNOS to total eNOS in the medulla. ATV also inhibited Rho-kinase activity and enhanced Akt activity in the kidney of SHRs.Conclusion ATV upregulates eNOS and nNOS expressions with Rho-kinase inhibition and Akt activation in the kidney of SHRs. The renal nitric oxide system, Rho-kinase and Akt may contribute to the antihypertensive and renoprotective effects of statins. J Hypertens 28: 2278-2288 (C) 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins.