title: Olmesartan induces renoprotective effects by stimulating angiotensin type 2 receptors and reducing oxidative stress in diabetic nephropathy.
abstract: BACKGROUND
  Angiotensin receptor blockers reduce the progression of diabetic nephropathy primarily by inhibiting angiotensin type 1 (AT(1)) receptors. In the present study, we investigated the role of angiotensin type 2 (AT(2)) receptors on the renoprotective effects of olmesartan in diabetic nephropathy.
  
  
  METHODS
  Six-week-old mice were treated with streptozotocin and divided into four groups: the OLM group (mice treated with olmesartan), the OLM+Ang II group (mice treated with olmesartan and angiotensin II), the OLM+PD group (mice treated with olmesartan and the AT(2) antagonist PD 123319), and the vehicle group. Nondiabetic mice were used as controls. We measured blood glucose levels and urinary excretions of albumin and 8-hydroxy-2'-deoxyguanosine (8-OHdG), which is a marker for oxidative stress.
  
  
  RESULTS
  Although urinary albumin excretion in the OLM and OLM+Ang II groups showed a tendency to be reduced compared to the vehicle group, it was significantly lower compared to the OLM+PD group. Urinary excretion of 8-OHdG was also significantly lower in the OLM and OLM+Ang II groups compared to the OLM+PD group.
  
  
  CONCLUSIONS
  In diabetic nephropathy, the renoprotective effects of olmesartan are due not only to the blockade of AT(1) receptors, but also to a reduction in oxidative stress via stimulation of AT(2) receptors.
authors.affiliation: Second Department of Internal Medicine, Kansai Medical University, Moriguchi City, Japan. jof@takii.kmu.ac.jp
authors.forename: Fusakazu
authors.initials: F
authors.lastname: Jo
authors.forename: Satoshi
authors.initials: S
authors.lastname: Morimoto
authors.forename: Mitsutaka
authors.initials: M
authors.lastname: Nakahigashi
authors.forename: Makiko
authors.initials: M
authors.lastname: Kusabe
authors.forename: Kazunori
authors.initials: K
authors.lastname: Someya
authors.forename: Tatsuyori
authors.initials: T
authors.lastname: Morita
authors.forename: Hiromi
authors.initials: H
authors.lastname: Jo
authors.forename: Takanobu
authors.initials: T
authors.lastname: Imada
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kosaki
authors.forename: Nagaoki
authors.initials: N
authors.lastname: Toyoda
authors.forename: Mitsushige
authors.initials: M
authors.lastname: Nishikawa
authors.forename: Toshiji
authors.initials: T
authors.lastname: Iwasaka
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use*; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000378:metabolism; D003928:Diabetic Nephropathies / Q000378:metabolism* / Q000517:prevention & control*; D007093:Imidazoles / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism; D044139:Receptor, Angiotensin, Type 2 / Q000819:agonists / Q000096:biosynthesis*; D013777:Tetrazoles / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D000975:Antioxidants; D007093:Imidazoles; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D013777:Tetrazoles; C437965:olmesartan