文章基本信息

标题：L-citrulline for protection of endothelial function from ADMA–induced injury in porcine coronary artery
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作者：Chao Xuan ; Li-Min Lun ; Jin-Xia Zhao 等
期刊名称：Scientific Reports
电子版ISSN：2045-2322
出版年度：2015
卷号：5
期号：1
DOI：10.1038/srep10987
语种：English
出版社：Springer Nature
摘要：Endogenous nitric oxide synthase (eNOS) inhibitor asymmetric dimethylarginine (ADMA) is a cardiovascular risk factor. We tested the hypothesis that L-citrulline may ameliorate the endothelial function altered by ADMA in porcine coronary artery (PCA). Myograph study for vasorelaxation, electrochemical measurement for NO, RT-PCR, and Western blot analysis for expression of eNOS, argininosuccinate synthetase (ASS), and p-eNOS^ser1177 were performed. cGMP was determined by enzyme immunoassay. Superoxide anion (O₂.⁻) production was detected by the lucigenin-enhanced chemiluminescence method. Compare with controls (96.03% ± 6.2%), the maximal relaxation induced by bradykinin was significantly attenuated (61.55% ± 4.8%, p 0.01), and significantly restored by L-citrulline (82.67 ± 6.4%, p 0.05) after 24 hours of ADMA exposure. Expression of eNOS, p-eNOS^ser1177, and ASS in PCA significantly increased after L-citrulline incubation. L-citrulline also markedly restored the NO production, and cGMP level which was reduced by ADMA. The increased O₂.⁻ production by ADMA was also inhibited by L-citrulline. L-citrulline restores the endothelial function in preparations treated with ADMA by preservation of NO production and suppression of O₂.⁻ generation. Preservation of NO is attributed to the upregulation of eNOS expression along with activation of p-eNOS^ser1177. L-citrulline improves endothelium-dependent vasodilation through NO/ cGMP pathway.