Blockade of Angiotensin II type-1 receptor reduces oxidative stress in adipose tissue and ameliorates adipocytokine dysregulation

Kidney Int. 2006 Nov;70(10):1717-24. doi: 10.1038/ Epub 2006 Sep 20.


Dysregulated production of adipocytokines may be involved in the development of atherosclerotic cardiovascular disease in metabolic syndrome and chronic kidney disease (CKD) associated with metabolic syndrome. The aim of this study was to determine the effects of treatment with angiotensin II (Ang II) type-1 receptor blocker (ARB) on the regulation of adipocytokines. Olmesartan, an ARB, significantly blunted the age- and body weight-associated falls in plasma adiponectin both in genetically and diet-induced obese mice, without affecting body weight, but had no effect on plasma adiponectin levels in lean mice. Olmesartan also ameliorated dysregulation of adipocytokines in obesity, such as tumor necrosis factor-alpha, plasminogen activator inhibitor-1, monocyte chemotactic protein-1, and serum amyloid A3. Olmesartan significantly reduced reactive oxygen species originating from accumulated fat and attenuated the expression of nicotinamide adenine dinucleotide phospho hydrogenase oxidase subunits in adipose tissue. In cultured adipocytes, olmesartan acted as an antioxidant and improved adipocytokine dysregulation. Our results indicate that blockade of Ang II receptor ameliorates adipocytokine dysregulation and that such action is mediated, at least in part, by targeting oxidative stress in obese adipose tissue. Ang II signaling and subsequent oxidative stress in adipose tissue may be potential targets for the prevention of atherosclerotic cardiovascular disease in metabolic syndrome and also in metabolic syndrome-based CKD.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adiponectin / metabolism*
  • Adipose Tissue / drug effects
  • Adipose Tissue / metabolism*
  • Angiotensin II / physiology
  • Angiotensin II Type 1 Receptor Blockers / pharmacology*
  • Animals
  • Atherosclerosis / physiopathology
  • Atherosclerosis / prevention & control
  • Cells, Cultured
  • Female
  • Gene Expression Regulation / drug effects
  • Gene Expression Regulation / genetics
  • Imidazoles / pharmacology*
  • Kidney Diseases / physiopathology
  • Kidney Diseases / prevention & control
  • Metabolic Syndrome / metabolism
  • Metabolic Syndrome / physiopathology
  • Mice
  • Mice, Inbred C57BL
  • Obesity / metabolism
  • Obesity / physiopathology
  • Oxidative Stress / drug effects*
  • Oxidative Stress / physiology
  • Plasminogen Activator Inhibitor 1 / genetics
  • Plasminogen Activator Inhibitor 1 / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Reactive Oxygen Species / metabolism
  • Serum Amyloid A Protein / genetics
  • Serum Amyloid A Protein / metabolism
  • Signal Transduction / physiology
  • Tetrazoles / pharmacology*
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / metabolism


  • Adiponectin
  • Angiotensin II Type 1 Receptor Blockers
  • Imidazoles
  • Plasminogen Activator Inhibitor 1
  • RNA, Messenger
  • Reactive Oxygen Species
  • Saa3 protein, mouse
  • Serum Amyloid A Protein
  • Tetrazoles
  • Tumor Necrosis Factor-alpha
  • Angiotensin II
  • olmesartan