Vascular angiotensin II type 2 receptor attenuates atherosclerosis via a kinin/NO-dependent mechanism.
INTRODUCTION
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.


MATERIALS AND 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.
['Takata|Hiroki|H|', 'Yamada|Hiroyuki|H|', 'Kawahito|Hiroyuki|H|', 'Kishida|Sou|S|', 'Irie|Daisuke|D|', 'Kato|Taku|T|', 'Wakana|Noriyuki|N|', 'Miyagawa|Sonoko|S|', 'Fukui|Kensuke|K|', 'Matsubara|Hiroaki|H|']
D000804:Angiotensin II D000818:Animals D001011:Aorta D001057:Apolipoproteins E D050197:Atherosclerosis D001920:Bradykinin D002118:Calcium D007705:Kinins D008264:Macrophages D008810:Mice, Inbred C57BL D008822:Mice, Transgenic D009000:Monocytes D019331:NG-Nitroarginine Methyl Ester D009569:Nitric Oxide D018384:Oxidative Stress D044139:Receptor, Angiotensin, Type 2 D013481:Superoxides D019010:Vascular Cell Adhesion Molecule-1
Angiotensin receptor atherosclerosis oxidative stress nitric oxide