Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan.
J Hypertens. 2010 Nov;28(11):2278-88. doi: 10.1097/HJH.0b013e32833e0924.
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).
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.
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.
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.
3-羟基-3-甲基戊二酰辅酶 A 还原酶抑制剂（他汀类药物）可降低血压，并对心血管和肾脏疾病有有益影响。本研究探讨了阿托伐他汀（ATV）慢性治疗对自发性高血压大鼠（SHR）肾脏中一氧化氮合酶（NOS）表达和 Rho-激酶及 Akt 活性的影响。
用 ATV 治疗 SHR 8 周，测量 SBP。通过免疫印迹分析检测肾脏中内皮型、神经元型和诱导型 NOS（eNOS、nNOS 和 iNOS）蛋白的表达。通过评估 eNOS、ezrin/radixin/moesin（ERM）和 Akt 的磷酸化来检测肾脏中 eNOS、Rho-激酶和 Akt 的活性。
ATV 降低了 SBP，而不改变血浆胆固醇水平。ATV 增加了皮质和髓质中的 eNOS 表达以及髓质中的 nNOS 表达，但不影响 iNOS 表达。尽管 ATV 增加了肾脏中的 eNOS 表达，但它降低了皮质中磷酸化 eNOS 的水平，并且不影响髓质中磷酸化 eNOS 与总 eNOS 的比值。ATV 还抑制了 SHR 肾脏中的 Rho-激酶活性并增强了 Akt 活性。
ATV 通过抑制 Rho-激酶和激活 Akt 上调 SHR 肾脏中的 eNOS 和 nNOS 表达。肾脏中的一氧化氮系统、Rho-激酶和 Akt 可能有助于他汀类药物的降压和肾保护作用。
