Ueda Seiji, Yamagishi Sho-Ichi, Kaida Yusuke, Okuda Seiya
Division of Nephrology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan.
Nephrology (Carlton). 2007 Dec;12(6):582-90. doi: 10.1111/j.1440-1797.2007.00840.x.
Decreased nitric oxide (NO) production and/or impaired NO bioavailability may occur in patients with chronic kidney disease (CKD), and could contribute to the elevation of blood pressure, cardiovascular disease (CVD) and the progression of renal injury in these patients. However, the underlying molecular mechanisms for reduced NO action in patients with CKD remains to be elucidated. Asymmetric dimethylarginine (ADMA) is a naturally occurring L-arginine analogue found in plasma and various types of tissues, acting as an endogenous NO synthase inhibitor in vivo. Further, plasma level of ADMA is elevated in patients with CKD and found to be a strong biomarker or predictor for future cardiovascular events. In addition, plasma level of ADMA could predict the progression of renal injury in these patients as well. These findings suggest that elevation of ADMA may be a missing link between CVD and CKD. In this review, we discuss the molecular mechanisms for the elevation of ADMA and its pathophysiological role for CVD in high-risk patients, especially focusing on patients with CKD.
慢性肾脏病（CKD）患者可能会出现一氧化氮（NO）生成减少和/或NO生物利用度受损的情况，这可能导致这些患者血压升高、心血管疾病（CVD）以及肾损伤进展。然而，CKD患者中NO作用降低的潜在分子机制仍有待阐明。不对称二甲基精氨酸（ADMA）是一种天然存在于血浆和各种组织中的L-精氨酸类似物，在体内作为内源性NO合酶抑制剂发挥作用。此外，CKD患者的血浆ADMA水平升高，并且被发现是未来心血管事件的一个强有力的生物标志物或预测指标。另外，血浆ADMA水平也可以预测这些患者的肾损伤进展。这些发现表明，ADMA升高可能是CVD和CKD之间缺失的环节。在本综述中，我们讨论了ADMA升高的分子机制及其在高危患者，尤其是CKD患者中对CVD的病理生理作用。
