Protective Mechanism of Adenosine to the Rat Arterial Endothelial Dysfunction Induced by Hydrogen Peroxide

  • Lu Jun
    Department of Pharmacology, School of Medicine, Xi'an Jiaotong University
  • Zhu Shu-Ming
    Department of Pharmacology, School of Medicine, Xi'an Jiaotong University
  • Zang Wei-Jin
    Department of Pharmacology, School of Medicine, Xi'an Jiaotong University Key Laboratory of Environment and Genes Related to Diseases of Ministry of Education, School of Medicine, Xi'an Jiaotong University
  • Xu Xiao-Li
    Department of Pharmacology, School of Medicine, Xi'an Jiaotong University
  • Luo Hong-Li
    Department of Pharmacology, School of Medicine, Xi'an Jiaotong University
  • Yu Xiao-Jiang
    Department of Pharmacology, School of Medicine, Xi'an Jiaotong University
  • Wang Sheng-Peng
    Department of Pharmacology, School of Medicine, Xi'an Jiaotong University
  • Kong Shan-Shan
    Department of Pharmacology, School of Medicine, Xi'an Jiaotong University
  • Wu Jie
    Department of Pharmacology, School of Medicine, Xi'an Jiaotong University Department of Cardiovascular and Respiratory Medicine, Shiga University of Medical Science
  • Horie Minoru
    Department of Cardiovascular and Respiratory Medicine, Shiga University of Medical Science
  • Sun Lei
    Department of Pharmacology, School of Medicine, Xi'an Jiaotong University

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Abstract

This study was designed to examine the in vitro effects of adenosine (Ado) on hydrogen peroxide-induced endothelial dysfunction in rats. Endothelial dysfunction was induced by exposing isolated rat mesenteric arteries to hydrogen peroxide (0.5 mM) for 12 h using an organ culture system. The protective effects of adenosine were tested by exposing isolated mesenteric arteries to adenosine (3×10−7 mol/l, 10−6 mol/l, 3×10−6 mol/l)+hydrogen peroxide (0.5 mM) for 12 h. This exposure to hydrogen peroxide induced a significant concentration-dependent inhibition of endothelium-dependent relaxation (EDR). Coculture of segments of mesenteric artery with adenosine (3×10−7, 10−6, and 3×10−6 mol/l) attenuated the hydrogen peroxide-induced impairment of vasorelaxation. This impairment was accompanied by a reduction in nitrite/nitrate, nitric oxide (NO) synthase (NOS), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities and an increasing in malondislehyde (MDA) and lactate dehydrogenase (LDH) activities in the aorta. These results indicate that adenosine can be used to attenuate hydrogen peroxide-induced endothelial dysfunction, an effect that may be related to antioxidation, thus enhancing NO production by preventing the decrease in NOS.

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