title: Vascular angiotensin II type 2 receptor attenuates atherosclerosis via a kinin/NO-dependent mechanism.
abstract: BACKGROUND
  The angiotensin II (Ang II) type 1 receptor exerts pro-atherogenic action by augmenting oxidative stress, whereas the Ang II type 2 receptor (AT2)-mediated effect on atherosclerosis remains controversial.
  
  
  METHODS
  AT2 transgenic (AT2-Tg) mice, which overexpress AT2 in their vascular smooth muscle cells, were crossed with apoE-deficient (apoE(-/-)) mice to generate AT2 transgenic apoE(-/-) mice (AT2-Tg/apoE(-/-)).
  
  
  RESULTS
  A subpressor dose of Ang II infusion exaggerated atherosclerosis development in apoE(-/-) mice, which was markedly suppressed in AT2-Tg/apoE(-/-) mice. Inhibitors of nitric oxide (NO) synthase (L-NAME) or bradykinin type 2 receptor completely abolished AT2-mediated anti-atherogenic actions. The vascular cell adhesion molecule-1 expression levels and degree of monocyte/macrophage accumulation in the intima were also considerably reduced in AT2-Tg/apoE(-/-) mice; these phenomena were completely reversed by L-NAME treatment. Ang II infusion significantly enhanced the accumulation of dihydroethidium-positive mononuclear cells in the intima and mRNA expression levels of Nox2, a phagocytic cell-type NADPH oxidase subunit in apoE(-/-) mice, which was completely inhibited in AT2-Tg/apoE(-/-) mice.
  
  
  CONCLUSIONS
  Vascular AT2 stimulation exerts anti-atherogenic actions in an endothelial kinin/NO-dependent manner, and its anti-oxidative effect is likely to be exerted by inhibiting the accumulation of superoxide-producing mononuclear leukocytes.
authors.affiliation: Department of Cardiovascular Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Takata
authors.affiliation: Department of Cardiovascular Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan hiyamada@koto.kpu-m.ac.jp.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Yamada
authors.affiliation: Department of Cardiovascular Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kawahito
authors.affiliation: Department of Cardiovascular Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Sou
authors.initials: S
authors.lastname: Kishida
authors.affiliation: Department of Cardiovascular Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Irie
authors.affiliation: Department of Cardiovascular Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Taku
authors.initials: T
authors.lastname: Kato
authors.affiliation: Department of Cardiovascular Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Wakana
authors.affiliation: Department of Cardiovascular Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Sonoko
authors.initials: S
authors.lastname: Miyagawa
authors.affiliation: Department of Cardiovascular Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Kensuke
authors.initials: K
authors.lastname: Fukui
authors.affiliation: Department of Cardiovascular Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Matsubara
mesh_terms: D000804:Angiotensin II; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D001057:Apolipoproteins E / Q000172:deficiency / Q000378:metabolism; D050197:Atherosclerosis / Q000378:metabolism* / Q000473:pathology; D001920:Bradykinin / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D007705:Kinins / Q000378:metabolism*; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects; D044139:Receptor, Angiotensin, Type 2 / Q000378:metabolism*; D013481:Superoxides / Q000378:metabolism; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
chemical_list: D001057:Apolipoproteins E; D007705:Kinins; D044139:Receptor, Angiotensin, Type 2; D019010:Vascular Cell Adhesion Molecule-1; D013481:Superoxides; D000804:Angiotensin II; D009569:Nitric Oxide; C065679:icatibant; D001920:Bradykinin; D002118:Calcium; D019331:NG-Nitroarginine Methyl Ester
keywords: Angiotensin; atherosclerosis; nitric oxide; oxidative stress; receptor