title: L-citrulline for protection of endothelial function from ADMA-induced injury in porcine coronary artery.
abstract: 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.
authors.affiliation: Department of Clinical Laboratory, The Affiliated Hospital of Qingdao University, Qingdao, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Xuan
authors.affiliation: Department of Clinical Laboratory, The Affiliated Hospital of Qingdao University, Qingdao, China.
authors.forename: Li-Min
authors.initials: LM
authors.lastname: Lun
authors.affiliation: Department of Clinical Laboratory, The Affiliated Hospital of Qingdao University, Qingdao, China.
authors.forename: Jin-Xia
authors.initials: JX
authors.lastname: Zhao
authors.affiliation: Department of Clinical Laboratory, The Affiliated Hospital of Qingdao University, Qingdao, China.
authors.forename: Hong-Wei
authors.initials: HW
authors.lastname: Wang
authors.affiliation: Department of Neurology , The Second Affliated Hospital of HeBei Medical University, Shijiazhuang, China.
authors.forename: Jue
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Ultrasound, The Affiliated Hospital of Qingdao University, Qingdao, China.
authors.forename: Chun-Ping
authors.initials: CP
authors.lastname: Ning
authors.affiliation: The Key Laboratory of Hypertension, The Affiliated Hospital of Qingdao University, Qingdao, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Molecular Microbiology, Oslo University Hospital, Oslo, Norway.
authors.forename: Bei-Bei
authors.initials: BB
authors.lastname: Zhang
authors.affiliation: TEDA International Cardiovascular Hospital, Tianjin &The Affiliated Hospital of Hangzhou Normal University, Hangzhou, China.|Department of Surgery, Oregon Health and Science University, Portland, Oregon.
authors.forename: Guo-Wei
authors.initials: GW
authors.lastname: He
mesh_terms: D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives; D002317:Cardiovascular Agents / Q000494:pharmacology*; D002956:Citrulline / Q000494:pharmacology*; D003331:Coronary Vessels / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D006152:Cyclic GMP / Q000378:metabolism; D004353:Drug Evaluation, Preclinical; D004730:Endothelium, Vascular / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D013481:Superoxides / Q000378:metabolism; D034421:Sus scrofa; D057772:Vascular System Injuries / Q000139:chemically induced / Q000188:drug therapy / Q000201:enzymology
chemical_list: D002317:Cardiovascular Agents; D013481:Superoxides; D002956:Citrulline; C018524:N,N-dimethylarginine; D001120:Arginine; D052250:Nitric Oxide Synthase Type III; D006152:Cyclic GMP