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Melatonin ameliorates A ngiotensin II ‐induced vascular endothelial damage via its antioxidative properties
Author(s) -
Nakao Tomoko,
Morita Hiroyuki,
Maemura Koji,
Amiya Eisuke,
Inajima Tsukasa,
Saito Yuichiro,
Watanabe Masafumi,
Manabe Ichiro,
Kurabayashi Masahiko,
Nagai Ryozo,
Komuro Issei
Publication year - 2013
Publication title -
journal of pineal research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.881
H-Index - 131
eISSN - 1600-079X
pISSN - 0742-3098
DOI - 10.1111/jpi.12071
Subject(s) - melatonin , endocrinology , medicine , angiotensin ii , nadph oxidase , enos , receptor , chemistry , agonist , endothelial dysfunction , endothelium , reactive oxygen species , stimulation , pharmacology , biology , oxidative stress , nitric oxide , biochemistry , nitric oxide synthase
Melatonin is well known to have a beneficial effect on the cardiovascular system, but it remains to be elucidated whether melatonin has a therapeutic effect on the vascular damage induced by the potential vasoactive substance angiotensin II ( A ng II ). In this study, the effects of melatonin on A ng II ‐induced vascular endothelial damage were investigated. In cultured vascular endothelial cells, A ng II stimulation increased ROS generation and inhibited eNOS phosphorylation ( S er1177), both of which were clearly restored by pretreatment with melatonin. The translocation of p47 phox subunit of NADPH oxidase from the cytosol to plasma membrane was promoted in A ng II ‐treated vascular endothelial cells, which was canceled by melatonin pretreatment. In A ng II ‐infused rats, increased ROS generation in the aortic wall and impaired endothelial function of the aortic ring were observed, which were rescued by coadministration of melatonin. In vasculature, melatonin receptor agonist ramelteon had the antioxidative effect in the same manner as melatonin by itself. These findings suggest that melatonin directly ameliorates A ng II ‐induced vascular endothelial damage partly via its antioxidative properties, providing with us the potential rationale for clinical application of melatonin to the prevention from cardiovascular diseases.