Beneficial effects of losartan on vascular injury induced by advanced glycosylation end products and their receptors in spontaneous hypertension rats.
This study was designed to explore the role of losartan, an angiotensin II receptor blocker, in hypertensive injuries of blood vessels and the potential mechanisms related to the vascular advanced glycosylation end product (AGE)/receptor (RAGE) system, oxidative stress and endothelial proinflammatory factors. Spontaneously hypertensive rats (SHR) were employed for our study, and age-matched Wistar-Kyoto rats (WKY) were used for control experiments. After losartan treatment for 12 weeks, we observed by immunofluorescence that the vascular AGE level in the losartan group was significantly lower than that of the SHR group and that the vascular mRNA expression of RAGE, NF-kappaB, NADPH oxidase p47phox and ET-1, as detected by RT-PCR, was significantly lower in losartan group than in the SHR group. Meanwhile, we found that the expression of RAGE and NF-kappaB proteins in the losartan group and the WKY group was remarkably lower than that of the SHR group. Compared with the SHR group, the activities of plasma superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX) and the NO level were robustly increased, while the plasma malondialdehyde (MDA) and ET-1 were substantially reduced. These findings suggest that losartan decreases the vascular AGE level, suppresses RAGE and NF-kappaB activation, and enhances the antioxidant capacity thereby improving the endothelial function, which induce hypertensive vascular remodeling.
Zhu
Wei-Wei
WW
Department of Geratology, Shandong Provincial Hospital of Shandong University, No. 324 Road, Jinan, Shandong, P.R. China.
Liu
Xue-Ping
XP
Wu
Nan
N
Zhao
Ting-Ting
TT
Zhao
Yong
Y
Zhang
Jie
J
Shao
Jian-Hua
JH
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001808:Blood Vessels / Q000473:pathology / Q000502:physiology; D001835:Body Weight / Q000187:drug effects; D042783:Endothelial Cells / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D017127:Glycation End Products, Advanced / Q000009:adverse effects* / Q000378:metabolism; D006339:Heart Rate / Q000187:drug effects; D006973:Hypertension / Q000150:complications / Q000473:pathology* / Q000503:physiopathology; D019808:Losartan / Q000494:pharmacology*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D019255:NADPH Oxidases / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D012038:Regeneration / Q000187:drug effects; D014652:Vascular Diseases / Q000139:chemically induced* / Q000473:pathology / Q000503:physiopathology
D017127:Glycation End Products, Advanced; D012333:RNA, Messenger; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D019255:NADPH Oxidases; C060505:neutrophil cytosolic factor 1; D019808:Losartan