title: Vascular VPO1 expression is related to the endothelial dysfunction in spontaneously hypertensive rats.
abstract: Reactive oxygen species (ROS) contributes to endothelial dysfunction that is involved in the pathogeneses of hypertension. Vascular peroxidase 1 (VPO1) can utilize ROS to catalyze peroxidative reactions, possibly enhancing endothelial dysfunction. This study is to identify VPO1's involvement in endothelial dysfunction and hypertension. Sixty-four spontaneously hypertensive rats (SHRs) and 64 age-matched, bodyweight controlled normotensive Wistar-Kyoto rats (WKYs) were randomly grouped and studied at the age of 5, 8, 13 and 20 weeks (16 animals, each). Blood pressure and vasodilator responses to acetylcholine in aortic rings were observed. The expressions of VPO1 and endothelial NO synthase (eNOS) in aortas were assessed by quantitative reverse transcription-PCR and western blotting analysis. Plasma concentrations of hydrogen peroxide (H2O2) and NO, NOX activity, hypochlorous acid (HOCl) production, and 3-nitrotyrosine content in aortic homogenates were also determined in this study. Along with the development of hypertension in SHR rats, VPO1 expression was up-regulated together with a significant increase in NOX activity, HOCl production, 3-nitrotyrosine content, and plasma H2O2 level compared with WKYs at 8, 13 and 20 weeks of age. In contrast, blood NO levels were decreased and aortic relaxation to acetylcholine was deteriorated in SHRs. The over-expression of VPO1 during the development of hypertension, accompanied by the endothelial dysfunction, the decreased NO levels, the elevated NOX and ROS activities, indicates a clear connection between VPO1 gene and hypertension. VPO1 may pathogenetically contribute to hypertension via signal pathways involving NOX-H2O2-VPO1-HOCl or JNK/p38 MAPK although further studies are needed to determine the precise mechanisms.
authors.affiliation: Department of Cardiovascular Medicine, Xiangya Hospital, Central South University, Changsha 410008, China.
authors.forename: Lizhen
authors.initials: L
authors.lastname: Yang
authors.forename: Yongping
authors.initials: Y
authors.lastname: Bai
authors.forename: Niansheng
authors.initials: N
authors.lastname: Li
authors.forename: Changping
authors.initials: C
authors.lastname: Hu
authors.forename: Jun
authors.initials: J
authors.lastname: Peng
authors.forename: Guangjie
authors.initials: G
authors.lastname: Cheng
authors.forename: Guogang
authors.initials: G
authors.lastname: Zhang
authors.forename: Ruizheng
authors.initials: R
authors.lastname: Shi
mesh_terms: D000818:Animals; D004730:Endothelium, Vascular / Q000378:metabolism / Q000503:physiopathology*; D006420:Hemeproteins / Q000235:genetics* / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000378:metabolism; D006997:Hypochlorous Acid / Q000378:metabolism; D008297:Male; D019001:Nitric Oxide Synthase / Q000378:metabolism; D010544:Peroxidases / Q000235:genetics* / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D006420:Hemeproteins; D017382:Reactive Oxygen Species; D006997:Hypochlorous Acid; D006861:Hydrogen Peroxide; C573339:vascular peroxidase, rat; D010544:Peroxidases; D019001:Nitric Oxide Synthase; D048051:p38 Mitogen-Activated Protein Kinases
keywords: Endothelia dysfunction; Hypertension; Hypochlorous acid; NADPH oxidase (NOX); Nitric oxide (NO); Vascular peroxidase 1