PMID- 11723025
OWN - NLM
STAT- MEDLINE
DCOM- 20020131
LR  - 20190623
IS  - 1524-4539 (Electronic)
IS  - 0009-7322 (Linking)
VI  - 104
IP  - 22
DP  - 2001 Nov 27
TI  - 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.
PG  - 2716-21
AB  - BACKGROUND: To investigate the effect of angiotensin (Ang) II type 1 receptor 
      (AT(1)) blocker on vascular remodeling and explore the possibility of the 
      involvement of Ang II type 2 receptor (AT(2)) stimulation in this process, we 
      examined the effects of the selective AT(1) blocker valsartan on the vascular 
      injury in wild-type (Agtr2+) and AT(2)-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. kg(-1). 
      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-1beta; and 
      infiltration of CD45-positive leukocytes and macrophages in the injured arteries 
      and further enhanced them in Agtr2- mice, suggesting the antagonistic effects of 
      AT(1) and AT(2) for vascular inflammation. Valsartan attenuated the expression of 
      MCP-1, TNF-alpha, IL-6, IL-1beta, 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 
      AT(2) receptor after AT(1) blockade is important in the improvement of the 
      inflammatory vascular injury.
FAU - Wu, L
AU  - Wu L
AD  - Department of Medical Biochemistry, Ehime University School of Medicine, Ehime, 
      Japan.
FAU - Iwai, M
AU  - Iwai M
FAU - Nakagami, H
AU  - Nakagami H
FAU - Li, Z
AU  - Li Z
FAU - Chen, R
AU  - Chen R
FAU - Suzuki, J
AU  - Suzuki J
FAU - Akishita, M
AU  - Akishita M
FAU - de Gasparo, M
AU  - de Gasparo M
FAU - Horiuchi, M
AU  - Horiuchi M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Circulation
JT  - Circulation
JID - 0147763
RN  - 0 (Angiotensin Receptor Antagonists)
RN  - 0 (Antihypertensive Agents)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Interleukin-1)
RN  - 0 (Interleukin-6)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptor, Angiotensin, Type 1)
RN  - 0 (Receptor, Angiotensin, Type 2)
RN  - 0 (Receptors, Angiotensin)
RN  - 0 (Tetrazoles)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 11128-99-7 (Angiotensin II)
RN  - 80M03YXJ7I (Valsartan)
RN  - 9041-90-1 (Angiotensin I)
RN  - EC 3.1.3.48 (Leukocyte Common Antigens)
RN  - EC 3.1.3.48 (Protein Tyrosine Phosphatase, Non-Receptor Type 1)
RN  - HG18B9YRS7 (Valine)
SB  - IM
MH  - Angiotensin I/genetics/metabolism
MH  - Angiotensin II/genetics/metabolism
MH  - *Angiotensin Receptor Antagonists
MH  - Animals
MH  - Antihypertensive Agents/pharmacology
MH  - Blood Pressure/drug effects
MH  - Cell Division/drug effects
MH  - Chemokine CCL2/metabolism
MH  - Femoral Artery/drug effects/*metabolism/pathology
MH  - Inflammation/drug therapy/*metabolism/pathology
MH  - Interleukin-1/metabolism
MH  - Interleukin-6/metabolism
MH  - Leukocyte Common Antigens/metabolism
MH  - Leukocytes/metabolism/pathology
MH  - Macrophages/metabolism/pathology
MH  - Male
MH  - Mice
MH  - Mice, Knockout
MH  - Muscle, Smooth, Vascular/drug effects/metabolism/pathology
MH  - Protein Tyrosine Phosphatase, Non-Receptor Type 1
MH  - RNA, Messenger/metabolism
MH  - Receptor, Angiotensin, Type 1
MH  - Receptor, Angiotensin, Type 2
MH  - Receptors, Angiotensin/deficiency/genetics/*metabolism
MH  - Tetrazoles/*pharmacology
MH  - Tumor Necrosis Factor-alpha/metabolism
MH  - Tunica Intima/drug effects/metabolism/pathology
MH  - Valine/analogs & derivatives/*pharmacology
MH  - Valsartan
EDAT- 2001/11/28 10:00
MHDA- 2002/02/01 10:01
CRDT- 2001/11/28 10:00
PHST- 2001/11/28 10:00 [pubmed]
PHST- 2002/02/01 10:01 [medline]
PHST- 2001/11/28 10:00 [entrez]
AID - 10.1161/hc4601.099404 [doi]
PST - ppublish
SO  - Circulation. 2001 Nov 27;104(22):2716-21. doi: 10.1161/hc4601.099404.