Mels Catharina M C, Huisman Hugo W, Smith Wayne, Schutte Rudolph, Schwedhelm Edzard, Atzler Dorothee, Böger Rainer H, Ware Lisa J, Schutte Aletta E
Hypertension in Africa Research Team (HART), North-West University, Private Bag X6001, Potchefstroom, 2520, South Africa.
MRC Research Unit for Hypertension and Cardiovascular Disease, North-West University, Potchefstroom, South Africa.
Age (Dordr). 2016 Feb;38(1):9. doi: 10.1007/s11357-016-9873-6. Epub 2016 Jan 14.
Inadequate substrate availability and increased nitric oxide synthase inhibitor levels attenuate nitric oxide (NO) synthesis, whereas increased vascular oxidative stress may lead to inactivation of NO. We compared markers of NO synthesis capacity and oxidative stress in a bi-ethnic male population. Inter-relationships of ambulatory blood pressure and urinary albumin-to-creatinine ratio with NO synthesis capacity and oxidative stress markers were investigated. NO synthesis capacity markers (L-arginine, asymmetric dimethylarginine (ADMA), and symmetric dimethylarginine (SDMA)) and oxidative stress markers (serum peroxides, total glutathione, glutathione peroxidase (GPx), glutathione reductase (GR), superoxide dismutase (SOD), and catalase) were measured. Black men displayed higher blood pressure and albumin-to-creatinine ratio (all p < 0.001), while NO synthesis capacity was more favorable (higher L-arginine and lower ADMA (p ≤ 0.003)). Antioxidant enzyme activities were similar except for the redox status markers (GR activity and GR/GPx ratio), which were upregulated in black men (p < 0.001). In black men, ADMA was inversely related to GPx activity (R (2) = 0.15; β = -0.20; p = 0.050) and GPx/SOD ratio (R (2) = 0.24; β = -0.37; p < 0.001), but none of these markers related to blood pressure or albumin-to-creatinine ratio. In white men, albumin-to-creatinine ratio was positively associated with ADMA (R (2) = 0.18; β = 0.39; p < 0.001) while ADMA was inversely related to GR activity (R (2) = 0.26; β = -0.29; p = 0.002) and GR/GPx ratio (R (2) = 0.25; β = -0.28; p = 0.003). Black men with elevated blood pressure and albumin-to-creatinine ratio displayed a favorable NO synthesis capacity. This may be counteracted by increased inactivation of NO, although it was not linked to vascular or renal phenotypes. In white men, reduced NO synthesis capacity may lower NO bio-availability, thereby influencing the albumin-to-creatinine ratio.
底物供应不足和一氧化氮合酶抑制剂水平升高会减弱一氧化氮(NO)的合成,而血管氧化应激增加可能导致NO失活。我们比较了双种族男性人群中NO合成能力和氧化应激的标志物。研究了动态血压和尿白蛋白与肌酐比值与NO合成能力和氧化应激标志物之间的相互关系。测量了NO合成能力标志物(L-精氨酸、不对称二甲基精氨酸(ADMA)和对称二甲基精氨酸(SDMA))和氧化应激标志物(血清过氧化物、总谷胱甘肽、谷胱甘肽过氧化物酶(GPx)、谷胱甘肽还原酶(GR)、超氧化物歧化酶(SOD)和过氧化氢酶)。黑人男性的血压和白蛋白与肌酐比值较高(所有p<0.001),而NO合成能力更有利(L-精氨酸较高且ADMA较低(p≤0.003))。除了氧化还原状态标志物(GR活性和GR/GPx比值)在黑人男性中上调(p<0.001)外,抗氧化酶活性相似。在黑人男性中,ADMA与GPx活性呈负相关(R(2)=0.15;β=-0.20;p=0.050)和GPx/SOD比值呈负相关(R(2)=0.24;β=-0.37;p<0.001),但这些标志物均与血压或白蛋白与肌酐比值无关。在白人男性中,白蛋白与肌酐比值与ADMA呈正相关(R(2)=0.18;β=0.39;p<0.001),而ADMA与GR活性呈负相关(R(2)=0.26;β=-0.29;p=0.002)和GR/GPx比值呈负相关(R(2)=0.25;β=-0.28;p=0.003)。血压和白蛋白与肌酐比值升高的黑人男性表现出良好的NO合成能力。尽管这与血管或肾脏表型无关,但可能会因NO失活增加而受到抵消。在白人男性中,NO合成能力降低可能会降低NO的生物利用度,从而影响白蛋白与肌酐比值。