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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.
Circulation. 2001 Nov 27; 104(22):2716-21.Circ

Abstract

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.

Authors+Show Affiliations

Department of Medical Biochemistry, Ehime University School of Medicine, Ehime, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

11723025

Citation

Wu, L, et al. "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." Circulation, vol. 104, no. 22, 2001, pp. 2716-21.
Wu L, Iwai M, Nakagami H, et al. 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. Circulation. 2001;104(22):2716-21.
Wu, L., Iwai, M., Nakagami, H., Li, Z., Chen, R., Suzuki, J., Akishita, M., de Gasparo, M., & Horiuchi, M. (2001). 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. Circulation, 104(22), 2716-21.
Wu L, et al. 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. Circulation. 2001 Nov 27;104(22):2716-21. PubMed PMID: 11723025.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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. AU - Wu,L, AU - Iwai,M, AU - Nakagami,H, AU - Li,Z, AU - Chen,R, AU - Suzuki,J, AU - Akishita,M, AU - de Gasparo,M, AU - Horiuchi,M, PY - 2001/11/28/pubmed PY - 2002/2/1/medline PY - 2001/11/28/entrez SP - 2716 EP - 21 JF - Circulation JO - Circulation VL - 104 IS - 22 N2 - 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. SN - 1524-4539 UR - https://www.unboundmedicine.com/medline/citation/11723025/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_ L2 - https://www.ahajournals.org/doi/10.1161/hc4601.099404?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -