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首页> 外文期刊>The journal of sexual medicine >Reversal of voltage-dependent erectile responses in the Zucker obese-diabetic rat by rosuvastatin-altered RhoA/Rho-kinase signaling.
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Reversal of voltage-dependent erectile responses in the Zucker obese-diabetic rat by rosuvastatin-altered RhoA/Rho-kinase signaling.

机译：瑞舒伐他汀改变的RhoA / Rho激酶信号转导逆转祖克肥胖糖尿病大鼠的电压依赖性勃起反应。

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INTRODUCTION: The combination of independent risk factors for erectile dysfunction, obesity, hypertension, and diabetes are collectively manifested in a condition known as metabolic syndrome X (MSX). However, the regulatory mechanisms responsible for the erectile dysfunction (ED) are not fully understood. Clinical studies suggest that a pleiotropic effect of statin's ability to enhance vascular relaxation might be through an impact on nitric oxide signaling or through a regulation of RhoA activation. AIM: We hypothesized that regulatory aspects of short-term statin therapy involve the alteration of the RhoA/Rho-kinase signaling cascade and will reverse the ED seen in a rat model of MSX. MAIN OUTCOME MEASURES: The magnitude and sensitivity of the voltage-dependent maintenance of intracavernosal blood pressure and mean arterial blood pressure. These responses were correlated with tissue protein and mRNA expression levels of RhoA and Rho kinases. METHODS: Erectile function was evaluated by assessing voltage-dependent stimulation of the cavernosal nerve in 16-20 weeks old lean and obese-diabetic Zucker rats treated with 5 mg/kg/day of rosuvastatin intraperitoneally for 3 days. Cavernosal tissue RhoA and Rho-kinases expression levels were evaluated by real-time reverse transcriptase-polymerase chain reaction, Western blot. RESULTS: The voltage-dependent erectile responses were suppressed by >30% in the obese-diabetic Zucker rat. The 3-day treatment with rosuvastatin partially restored the erectile response. The Rho-kinase inhibitor, H-1152, dose dependently increased the erectile responses and shifted the voltage sensitivity with statin treatment. Analysis of protein expression levels suggested elevation of RhoA and Rho kinases in obese-diabetics and statin treatment lowering Rho-kinase II. The RhoA and Rho-kinase II mRNA levels were significantly reduced in the rosuvastatin-treated obese-diabetic animals. CONCLUSIONS: These results support a hypothesis that short-term statin therapy may lower RhoA/Rho-kinase expression levels and improve cavernosal blood pressure response to Rho-kinase inhibition and voltage-stimulation, and reversing an augmented vasoconstricted state associated with diabetes and/or hypertension in MSX.
机译：简介：勃起功能障碍，肥胖，高血压和糖尿病的独立危险因素共同存在于被称为代谢综合征X（MSX）的疾病中。但是，尚未完全了解引起勃起功能障碍（ED）的调节机制。临床研究表明，他汀类药物增强血管舒张能力的多效性可能是通过影响一氧化氮信号传导或通过调节RhoA激活来实现的。目的：我们假设短期他汀类药物治疗的调节方面涉及RhoA / Rho激酶信号级联的改变，并将逆转在MSX大鼠模型中观察到的ED。主要观察指标：海绵体内血压和平均动脉压的电压依赖性维持幅度和敏感性。这些反应与RhoA和Rho激酶的组织蛋白和mRNA表达水平相关。方法：通过评估腹腔注射瑞舒伐他汀5 mg / kg /天，16天，20周龄的肥胖和肥胖型糖尿病祖克大鼠对海绵体神经的电压依赖性刺激，评估勃起功能。海绵体组织RhoA和Rho激酶的表达水平通过实时逆转录聚合酶链反应，Western印迹进行了评估。结果：肥胖型糖尿病祖克大鼠的电压依赖性勃起反应被抑制> 30％。瑞舒伐他汀治疗3天可部分恢复勃起反应。 Rho激酶抑制剂H-1152剂量依赖性地增加勃起反应并通过他汀类药物治疗改变电压敏感性。蛋白质表达水平的分析表明，肥胖糖尿病患者中RhoA和Rho激酶升高，而他汀类药物治疗则降低Rho激酶II。在瑞舒伐他汀治疗的肥胖糖尿病动物中，RhoA和Rho激酶II mRNA水平显着降低。结论：这些结果支持一个假设，即短期他汀类药物疗法可降低RhoA / Rho激酶的表达水平，并改善海绵体血压对Rho激酶抑制和电压刺激的反应，并逆转与糖尿病和/或糖尿病相关的血管收缩状态的增强MSX中的高血压。

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