Schmieder Roland E
University of Erlangen/Nuremberg, Germany.
J Hypertens Suppl. 2006 Apr;24(2):S31-5. doi: 10.1097/01.hjh.0000220101.57896.cd.
Endothelial dysfunction, characterized by impaired nitric oxide activity, constitutes an early step in the pathogenesis of atherosclerotic disease. Prospective studies have shown that impaired endothelium-dependent vasorelaxation and the vasodilatory response of coronary arteries to acetylcholine predict cardiovascular events. Microalbuminuria and estimated glomerular filtration rate, which are both deeply influenced by renal nitric oxide activity, are predictors of cardiovascular outcome and total mortality but develop at a later stage of renal impairment. Endothelial dysfunction reflects early stage renal involvement in the atherosclerotic processes. The Telmisartan versus Ramipril in renal ENdothelium DYsfunction (TRENDY) trial examined endothelial function of the renal vasculature as a therapeutic target in patients with hypertension and type 2 diabetes, but without albuminuria. The rationale was that blockade of the renin-angiotensin system (RAS) is cardio- and renoprotective at later stages of the disease, but the impact of blockade of the RAS at earlier stages of disease is unknown. The results of TRENDY indicate that the endothelial function, as assessed by basal nitric oxide activity, can be improved after RAS blockade. These data complement the results of the Diabetics Exposed to Telmisartan And enalaprIL (DETAIL) trial, which demonstrated that telmisartan and enalapril similarly decelerate the progression of overt diabetic nephropathy. The results of TRENDY are in accordance with the observed changes in peripheral circulation. Endothelium-dependent vasorelaxation could be improved with angiotensin II receptor blockers, but not with diuretics or beta-blockers, in hypertensive patients. Intervention at the beginning of the renal and cardiovascular continuum offers the opportunity to prevent the fatal development towards renal and cardiac failure.
内皮功能障碍以一氧化氮活性受损为特征，是动脉粥样硬化性疾病发病机制的早期步骤。前瞻性研究表明，内皮依赖性血管舒张功能受损以及冠状动脉对乙酰胆碱的舒张反应可预测心血管事件。微量白蛋白尿和估计肾小球滤过率均受肾一氧化氮活性的深刻影响，是心血管结局和总死亡率的预测指标，但在肾功能损害的后期才会出现。内皮功能障碍反映了肾脏在动脉粥样硬化过程中的早期受累情况。替米沙坦与雷米普利治疗肾内皮功能障碍（TRENDY）试验将肾血管系统的内皮功能作为高血压和2型糖尿病患者（但无蛋白尿）的治疗靶点进行了研究。其基本原理是，在疾病后期阻断肾素-血管紧张素系统（RAS）具有心脏和肾脏保护作用，但在疾病早期阻断RAS的影响尚不清楚。TRENDY试验的结果表明，通过基础一氧化氮活性评估的内皮功能在阻断RAS后可以得到改善。这些数据补充了替米沙坦与依那普利治疗糖尿病（DETAIL）试验的结果，该试验表明替米沙坦和依那普利同样能减缓显性糖尿病肾病的进展。TRENDY试验的结果与外周循环中观察到的变化一致。在高血压患者中，血管紧张素II受体阻滞剂可改善内皮依赖性血管舒张功能，而利尿剂或β受体阻滞剂则不能。在肾脏和心血管疾病连续体的早期进行干预，为预防向肾衰竭和心力衰竭的致命发展提供了机会。
