Yazici D, Yavuz D Gogas, Unsalan S, Toprak A, Yüksel M, Deyneli O, Aydin H, Tezcan H, Rollas S, Akalin S
Section of Endocrinology and Metabolism, Marmara University Medical School, Istanbul, Turkey.
J Endocrinol Invest. 2007 Oct;30(9):726-33. doi: 10.1007/BF03350809.
Increased asymmetrical dimethylarginine (ADMA) is known to disturb endothelial function. ACE inhibitors decrease plasma ADMA levels in diseases associated with endothelial dysfunction. The effects of ACE inhibition on endothelial function and plasma ADMA levels in Type 1 diabetic patients was evaluated in the study.
Thirty Type 1 diabetic patients [29+/-6 yr; females (F)/males (M): 18/12] and 29 controls (30+/-6 yr; F/M: 16/13) were recruited. Flow-mediated dilatation (FMD), plasma ADMAand thiobarbituric acid reactive substances (TBARs) were determined at baseline, on day 15 and 90 of 0.5 mg qd trandolapril therapy.
Compared to controls, baseline FMD levels were lower (4.7+/-2.0% vs 11.2+/-3.9%) (p<0.001), plasma ADMA (271.1+/-48.1 nmol/l vs 237.5+/-25.1 nmol/l) (p<0.05) and TBARs levels [4517.1+/-2366.9 nmol/malondialdehyde (MDA) vs 1775.9+/-598.7 nmol/MDA] (p<0.001) were higher in diabetic patients. On day 90 of trandolapril treatment, FMD (8.6+/-4.1%) (p<0.01) increased, ADMA levels (229.6+/-42.9 nmol/l) (p<0.001) decreased and TBARs levels (1531.8+/-1036.0 nmol/MDA) (p<0.001) decreased significantly. FMD was negatively correlated with plasma ADMA (r=-0.228, p<0.01), and TBARs levels (r=-0.244, p=0.02), whereas ADMA and TBARs levels were correlated positively (r=0.399, p<0.0001).
In conclusion, endothelial dysfunction is associated with elevated plasma ADMA levels in Type 1 diabetic patients. Low-dose ACE inhibition improves endothelial dysfunction and reduces ADMA levels. The antioxidant action of ACE inhibitors may play role in this process.
已知不对称二甲基精氨酸（ADMA）水平升高会干扰内皮功能。在与内皮功能障碍相关的疾病中，血管紧张素转换酶（ACE）抑制剂可降低血浆ADMA水平。本研究评估了ACE抑制对1型糖尿病患者内皮功能和血浆ADMA水平的影响。
招募了30例1型糖尿病患者[29±6岁；女性（F）/男性（M）：18/12]和29例对照者（30±6岁；F/M：16/13）。在基线时、服用0.5mg每日一次群多普利治疗的第15天和第90天，测定血流介导的血管舒张功能（FMD）、血浆ADMA和硫代巴比妥酸反应性物质（TBARs）。
与对照者相比，糖尿病患者的基线FMD水平较低（4.7±2.0%对11.2±3.9%）（p<0.001），血浆ADMA水平较高（271.1±48.1nmol/L对237.5±25.1nmol/L）（p<0.05），TBARs水平较高[4517.1±2366.9nmol/丙二醛（MDA）对1775.9±598.7nmol/MDA]（p<0.001）。在群多普利治疗的第90天，FMD（8.6±4.1%）（p<0.01）升高，ADMA水平（229.6±42.9nmol/L）（p<0.001）降低，TBARs水平（1531.8±1036.0nmol/MDA）（p<0.001）显著降低。FMD与血浆ADMA呈负相关（r=-0.228，p<0.01），与TBARs水平呈负相关（r=-0.244，p=0.02），而ADMA与TBARs水平呈正相关（r=0.399，p<0.0001）。
总之，1型糖尿病患者的内皮功能障碍与血浆ADMA水平升高有关。低剂量ACE抑制可改善内皮功能障碍并降低ADMA水平。ACE抑制剂的抗氧化作用可能在此过程中起作用。
