Key result
ADMA concentrations greater than 10 μM increased oxidative stress in human umbilical vein endothelial cells, a process involving the cationic transport system and eNOS uncoupling.
ADMA-induced vascular oxidative stress involves the cationic transport system and eNOS uncoupling rather than the Ang II-NADPH oxidase pathway.
Challenges Ang II-NADPH oxidase primacy in ADMA oxidative stress; hypothesis-generating for eNOS-targeted research in endothelial dysfunction.
The mechanism by which asymmetric dimethylarginine (ADMA) induces vascular oxidative stress is not well understood. In this study, we utilized human umbilical vein endothelial cells (HUVEC) to examine the roles of ADMA cellular transport and the uncoupling of endothelial nitric oxide synthase (eNOS) in contributing to this phenomenon. Dihydroethidium (DHE) fluorescence was used as an index of oxidative stress. Whole cells and their isolated membrane fractions exhibited measureable increased DHE fluorescence at ADMA concentrations greater than 10 μM. ADMA-induced DHE fluorescence was inhibited by co-incubation with L-lysine, tetrahydrobiopterin (BH(4)), or L-nitroarginine methyl ester (L-NAME). Oxidative stress induced in these cells by angiotensin II (Ang II) were unaffected by the same concentrations of L-lysine, L-NAME and BH(4). ADMA-induced reduction in cellular nitrite or nitrite/nitrate production was reversed in the presence of increasing concentrations of BH(4). These results suggest that ADMA-induced DHE fluorescence involves the participation of both the cationic transport system in the cellular membrane and eNOS instead of the Ang II-NADPH oxidase pathway.
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Mohan et al. (2012) studied Vascular oxidative stress. Asymmetric dimethylarginine (ADMA) was evaluated on Dihydroethidium (DHE) fluorescence (index of oxidative stress). ADMA concentrations greater than 10 μM increased oxidative stress in human umbilical vein endothelial cells, a process involving the cationic transport system and eNOS uncoupling.
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