Division of Nephrology, Toronto General Hospital and Banting and Best Diabetes Centre, University of Toronto, Toronto, Ontario, Canada.
Kidney Int. 2013 Dec;84(6):1246-53. doi: 10.1038/ki.2013.221. Epub 2013 Jun 12.
Animal studies suggest temporary renin-angiotensin system (RAS) blockade enhances long-term vascular protective effects; however, this is not established in humans. Here we evaluated the long-term effects of prior RAS blockade on hemodynamic function, urinary measures of inflammation, and tissue antioxidant mRNA expression in patients with type 1 diabetes mellitus (T1DM) who participated in the 5-year Renin Angiotensin System Study (RASS). At 4 years after completing the RASS and discontinuing study medication, renal hemodynamic responses to clamped hyperglycemia were significantly greater in 18 patients in the RAS blockade group compared to 9 patients of the placebo-treated group. Individuals who had received RAS blockade also exhibited higher flow-mediated vasodilatation, reduced urinary cytokine excretion in response to hyperglycemia, and increased skin mRNA expression of superoxide dismutase-1 and catalase. Thus, patients with uncomplicated T1DM who received prior RAS blockade for 5 years maintain long-term effects on renal hemodynamic and systemic vascular function, inflammatory pathways in the kidney, and antioxidant enzyme expression in skin 4 years after discontinuation of therapy. Our findings suggest that sustained long-term protective effects of finite RAS inhibition requires further study.
动物研究表明，短暂的肾素-血管紧张素系统（RAS）阻断可增强长期的血管保护作用；然而，这在人类中尚未得到证实。在这里，我们评估了先前的 RAS 阻断对 1 型糖尿病（T1DM）患者的血流动力学功能、尿炎症标志物以及组织抗氧化 mRNA 表达的长期影响，这些患者参加了为期 5 年的肾素-血管紧张素系统研究（RASS）。在完成 RASS 并停止研究药物治疗 4 年后，与安慰剂治疗组的 9 名患者相比，RAS 阻断组的 18 名患者的肾脏对高血糖的血流动力学反应明显更大。接受 RAS 阻断治疗的患者还表现出更高的血流介导的血管舒张、对高血糖的尿细胞因子排泄减少，以及皮肤中超氧化物歧化酶-1 和过氧化氢酶的 mRNA 表达增加。因此，接受 5 年 RAS 阻断治疗的无并发症 T1DM 患者在停止治疗 4 年后，仍然保持着对肾脏血流动力学和全身血管功能、肾脏炎症途径以及皮肤抗氧化酶表达的长期影响。我们的发现表明，有限的 RAS 抑制的持续长期保护作用需要进一步研究。
