Roles of Angiotensin II Type 2 Receptor Stimulation Associated With Selective Angiotensin II Type 1 Receptor Blockade With Valsartan in the Improvement of Inflammation-Induced Vascular Injury.
Wu, Lan MD; Iwai, Masaru MD, PhD; Nakagami, Hironori MD; Li, Zhen MD; Chen, Rui MD; Suzuki, Jun MD; Akishita, Masahiro MD, PhD; de Gasparo, Marc MD, PhD; Horiuchi, Masatsugu MD, PhD
[Report]
Circulation.
104(22):2716-2721, November 27, 2001.
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Background-: To investigate the effect of angiotensin (Ang) II type 1 receptor (AT1) blocker on vascular remodeling and explore the possibility of the involvement of Ang II type 2 receptor (AT2) stimulation in this process, we examined the effects of the selective AT1 blocker valsartan on the vascular injury in wild-type (Agtr2 ) and AT2-null (Agtr2-) mice.
Methods and Results-: Neointima formation and the proliferation of vascular smooth muscle cells (VSMCs) induced by cuff placement on the femoral artery were greater in Agtr2- mice than those in Agtr2 mice. Treatment of mice with valsartan at a dose of 1 mg [middle dot] kg-1 [middle dot] d-1, which did not influence systolic blood pressure, significantly decreased neointima formation and the proliferation of VSMCs, whereas the valsartan was less effective in Agtr2- mice. Moreover, cuff placement increased the expression of monocyte chemoattractant protein-1 (MCP-1); inflammatory cytokines such as tumor necrosis factor (TNF)-[alpha], interleukin (IL)-6, and IL-1[beta]; and infiltration of CD45-positive leukocytes and macrophages in the injured arteries and further enhanced them in Agtr2- mice, suggesting the antagonistic effects of AT1 and AT2 for vascular inflammation. Valsartan attenuated the expression of MCP-1, TNF-[alpha], IL-6, IL-1[beta], and infiltration of leukocytes and macrophages in the injured arteries; however, these effects of valsartan were less prominent in Agtr2- mice.
Conclusions-: These results suggest that the stimulation of the AT2 receptor after AT1 blockade is important in the improvement of the inflammatory vascular injury.
(C) 2001 American Heart Association, Inc.
