Bergamini Stefania, Vandelli Lorenza, Bellei Elisa, Rota Cristina, Manfredini Paolo, Tomasi Aldo, Albertazzi Alberto, Iannone Anna
Department of Biomedical Sciences, University of Modena and Reggio Emilia, Modena, Italy.
Nitric Oxide. 2004 Nov;11(3):273-8. doi: 10.1016/j.niox.2004.10.002.
Hypotension is one of the major complications in patients undergoing haemodialysis (HD), that is well evident in patients defined as "hypotension-prone." The mechanisms underlying the hypotensive episodes are not known. We carried out a clinical study on hypotension-prone HD patients to test the existence of a dysregulation in the nitric oxide (NO) generating pathway. Since asymmetric dimethylarginine (ADMA) is an endogenous compound which regulates NO synthesis, we measured its variation in plasma of stable-HD and hypotension-prone patients before, during, and at the end of HD. Before HD, the hypotension-prone patients have higher ADMA levels than stable-HD patients. The HD procedure significantly removes ADMA from plasma of stable-HD patients, while in the hypotension-prone ADMA levels are unchanged at the end of the HD. Moreover, in the hypotension-prone patients, during the hypotensive episode, a dramatic drop of ADMA levels is observed, followed by a rapid increase at the end of the HD. The symmetric dimethylarginine (SDMA), which has no effect on NO synthesis, is also high in plasma of both groups of HD patients compared to normal subjects, and in both groups its levels at the end of HD are significantly reduced. The hypotension-prone patients have basal TNF-alpha levels lower than the stable-HD groups, that significantly increase during the hypotensive episode. On the basis of these findings, we suggest that the hypotensive syndrome could be related to a dysregulation between ADMA metabolism and clearance due both to cytokines release and to an extremely fast ADMA clearance during HD, leading to an increase in NO blood levels.
低血压是血液透析（HD）患者的主要并发症之一，在被定义为“易发生低血压”的患者中表现得尤为明显。低血压发作的潜在机制尚不清楚。我们对易发生低血压的HD患者进行了一项临床研究，以测试一氧化氮（NO）生成途径中是否存在调节异常。由于不对称二甲基精氨酸（ADMA）是一种调节NO合成的内源性化合物，我们测量了稳定HD患者和易发生低血压患者在HD前、HD期间和HD结束时血浆中ADMA的变化。HD前，易发生低血压的患者ADMA水平高于稳定HD患者。HD过程显著降低了稳定HD患者血浆中的ADMA水平，而在易发生低血压的患者中，HD结束时ADMA水平未发生变化。此外，在易发生低血压的患者中，在低血压发作期间，观察到ADMA水平急剧下降，随后在HD结束时迅速升高。对称二甲基精氨酸（SDMA）对NO合成没有影响，与正常受试者相比，两组HD患者血浆中的SDMA水平也较高，并且两组在HD结束时其水平均显著降低。易发生低血压的患者基础肿瘤坏死因子-α（TNF-α）水平低于稳定HD组，在低血压发作期间显著升高。基于这些发现，我们认为低血压综合征可能与ADMA代谢和清除之间的调节异常有关，这是由于细胞因子释放以及HD期间ADMA清除极快，导致血液中NO水平升高。
