Melatonin ameliorates Angiotensin II‐induced vascular endothelial damage via its antioxidative properties

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 (Ang II). In this study, the effects of melatonin on Ang II‐induced vascular endothelial damage were investigated. In cultured vascular endothelial cells, Ang II stimulation increased ROS generation and inhibited eNOS phosphorylation (Ser1177), 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 Ang II‐treated vascular endothelial cells, which was canceled by melatonin pretreatment. In Ang 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 Ang 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.