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L-citrulline for protection of endothelial function from ADMA–induced injury in porcine coronary artery
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L-citrulline for protection of endothelial function from ADMA–induced injury in porcine coronary artery
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L-citrulline for protection of endothelial function from ADMA–induced injury in porcine coronary artery
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Journal Article
L-citrulline for protection of endothelial function from ADMA–induced injury in porcine coronary artery
2015
Overview
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 (O
2
.
−
) 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 O
2
.
−
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 O
2
.
−
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.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
/ 13/1
/ 13/95
/ 692/308
/ Animals
/ Arginine - analogs & derivatives
/ Cardiovascular Agents - pharmacology
/ Coronary Vessels - drug effects
/ Coronary Vessels - enzymology
/ Coronary Vessels - pathology
/ Drug Evaluation, Preclinical
/ Endothelium, Vascular - drug effects
/ Endothelium, Vascular - enzymology
/ Endothelium, Vascular - pathology
/ Humanities and Social Sciences
/ Nitric Oxide Synthase Type III - metabolism
/ Protein Processing, Post-Translational
/ Science
/ Vascular System Injuries - chemically induced
/ Vascular System Injuries - drug therapy
