Vascular VPO1 expression is related to the endothelial dysfunction in spontaneously hypertensive rats

Academic Article

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 20weeks (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 20weeks 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. © 2013 Elsevier Inc.
  • Authors

    Digital Object Identifier (doi)

    Author List

  • Yang L; Bai Y; Li N; Hu C; Peng J; Cheng G; Zhang G; Shi R
  • Start Page

  • 511
  • End Page

  • 516
  • Volume

  • 439
  • Issue

  • 4