title: Apelin-13 deteriorates hypertension in rats after damage of the vascular endothelium by ADMA.
abstract: Asymmetric dimethylarginine (ADMA) is a risk factor for endothelial dysfunction. The polypeptide apelin has biphasic effects on blood vessels in vivo and in vitro. We investigated the effect of apelin-13 on ADMA-damaged vessels. Rats were divided among ADMA-treated and control groups, which were treated with ADMA (10 mg·(kg body mass)(-1)·day(-1)) or saline, respectively, for 4 weeks. Systolic blood pressure (SBP) was measured before and after the injection of apelin-13. The ultrastructure of endothelial cells in caudal arteries was examined using transmission electron microscopy. The reactivities of isolated caudal artery rings were observed after exposure to apelin-13, and myosin light chain (MLC) phosphorylation was assessed by immunohistochemistry in rings treated with or without apelin-13. ADMA induced hypertension and endothelial dysfunction. After injection of apelin-13, SBP declined in the control group but was elevated in the ADMA-treated group. In vitro, apelin-13 caused relaxation in rings in the control group, but it contracted rings in the ADMA-treated group. Apelin-13 promoted MLC phosphorylation in vascular smooth muscle cells (VSMCs) in the ADMA group. These results indicate that apelin-13 might pass through ADMA-damaged endothelium and act on VSMCs to increase MLC phosphorylation, thus contributing to vasoconstriction and exacerbating hypertension.
authors.affiliation: Department of Nephrology, Affiliated Beijing Friendship Hospital, Faculty of Kidney Diseases, Capital Medical University, No. 95 Yong An Road, Xi Cheng District, Beijing 100050, China.
authors.forename: Xue
authors.initials: X
authors.lastname: Han
authors.forename: Dong-Liang
authors.initials: DL
authors.lastname: Zhang
authors.forename: Dao-Xin
authors.initials: DX
authors.lastname: Yin
authors.forename: Qi-Dong
authors.initials: QD
authors.lastname: Zhang
authors.forename: Wen-Hu
authors.initials: WH
authors.lastname: Liu
mesh_terms: D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives*; D001794:Blood Pressure / Q000187:drug effects*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D019332:Endothelin-1 / Q000097:blood; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology / Q000648:ultrastructure; D006973:Hypertension / Q000097:blood / Q000139:chemically induced* / Q000473:pathology / Q000503:physiopathology; D007275:Injections, Intravenous; D036341:Intercellular Signaling Peptides and Proteins / Q000008:administration & dosage / Q000633:toxicity*; D008297:Male; D018994:Myosin Light Chains / Q000378:metabolism; D009569:Nitric Oxide / Q000097:blood; D010766:Phosphorylation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014661:Vasoconstriction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects; D014841:von Willebrand Factor / Q000378:metabolism
chemical_list: D019332:Endothelin-1; D036341:Intercellular Signaling Peptides and Proteins; D018994:Myosin Light Chains; C495199:apelin-13 peptide; D014841:von Willebrand Factor; D009569:Nitric Oxide; C018524:N,N-dimethylarginine; D001120:Arginine