RT Journal Article
SR Electronic
T1 Synergistic Inhibitory Effect of Rosuvastatin and Angiotensin II Type 2 Receptor Agonist on Vascular Remodeling
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 352
OP 358
DO 10.1124/jpet.116.233148
VO 358
IS 2
A1 Hui-Yu Bai
A1 Masaki Mogi
A1 Hirotomo Nakaoka
A1 Harumi Kan-no
A1 Kana Tsukuda
A1 Xiao-Li Wang
A1 Bao-Shuai Shan
A1 Masayoshi Kukida
A1 Toshifumi Yamauchi
A1 Akinori Higaki
A1 Li-Juan Min
A1 Jun Iwanami
A1 Masatsugu Horiuchi
YR 2016
UL http://jpet.aspetjournals.org/content/358/2/352.abstract
AB We investigated the possibility that coadministration of rosuvastatin and compound 21 (C21), a selective angiotensin II type 2 (AT2) receptor agonist, could exert synergistic preventive effects on vascular injury. Vascular injury was induced by polyethylene cuff placement on the femoral artery in 9-week-old male C57BL/6J mice. Mice were treated with rosuvastatin and/or with C21 after cuff placement. Neointima formation was determined 14 days after the operation and cell proliferation, and superoxide anion production and expression of inflammatory cytokines were examined 7 days after cuff placement. Neointima formation was significantly attenuated by the treatment of rosuvastatin (5 mg kg−1 day−1) or C21 (10 μg kg−1 day−1), associated with the decreases in proliferating cell nuclear antigen (PCNA) labeling index, oxidative stress, and the expression of inflammatory markers. Treatment with a noneffective dose of rosuvastatin (0.5 mg kg−1 day−1) plus a low dose of C21 (1 μg kg−1 day−1) inhibited the PCNA labeling index, superoxide anion production, mRNA expressions of NAD(P)H subunits, and mRNA and protein expressions of inflammatory markers associated with marked inhibition of neointima formation. Angiotensin II type 1 (AT1) receptor mRNA expression did not differ the groups. By contrast, AT2 receptor mRNA expression was increased by administration of C21 at the dose of 10 μg kg−1 day−1 but not by C21 at the dose of 1 μg kg−1 day−1 or rosuvastatin. The combination of rosuvastatin and AT2 receptor agonist exerted synergistic preventive effects on vascular remodeling associated with the decreases in cell proliferation, oxidative stress, and inflammatory reaction. That could be a powerful approach to vascular disease prevention.