The angiotensin II receptor antagonist, losartan, enhances regulator of G protein signaling 2 mRNA expression in vascular smooth muscle cells of Wistar rats
机构：[1]Department of Cardiology, Fourth Hospital of Hebei Medical University, Shijiazhuang, China临床科室心血管内科河北医科大学第四医院[2]Department of Ophthalmology, University of Tokyo School of Medicine, Tokyo, Japan[3]Division of Clinical Nutrition, Faculty of Home Economics, Kyoritsu Women’s University, Tokyo, Japan[4]Institute of Medical Science, St Marianna University School of Medicine, Kawasaki, Japan
Angiotensin II (Ang II) reportedly enhances regulator of G-protein signaling 2 (RGS2), thus making a negative feedback loop for Ang II signal transduction. However, few studies have reported whether Ang II receptor (ATR) antagonists influence RGS2 mRNA expression. We investigated RGS2 mRNA expression when Ang II binding to ATR was blocked with Ang II subtype-1 receptor (AT(1)R) blockers using vascular smooth muscle cells from the thoracic aorta of male Wistar rats. RGS2 mRNA expression significantly increased with Ang II stimulation, and this increase was almost completely abolished by olmesartan, a potent AT(1)R-specific blocker. Ang II subtype-2 receptor (AT(2)R) was not involved in Ang II-mediated RGS expression. In contrast, the AT(1)R blocker, losartan, partially decreased Ang II-mediated RGS2 mRNA expression because this antagonist directly stimulated RGS2 mRNA expression in Ang II-free medium. EXP3174, which is an active metabolite of losartan, almost completely blunted Ang II-mediated RGS2 mRNA expression without direct stimulation of RGS2 mRNA expression. Moreover, pretreatment with olmesartan abolished Ang II-mediated RGS2 mRNA expression. Treatment with a protein kinase C inhibitor partially decreased losartan-mediated RGS2 mRNA expression. These results suggest that AT(1)R blockers inhibit RGS2 mRNA expression in response to Ang II via an AT(1)R-mediated mechanism. However, the AT(1)R blocker, losartan, behaves as a direct agonist for RGS2 mRNA expression via AT(1)R through protein kinase C-dependent and -independent pathways. In conclusion, losartan exhibits dual effects on RGS2 mRNA expression, and the direct upregulation of RGS2 mRNA expression may provide a new strategy for the treatment of hypertension.
基金：
This study was supported in part by a grant for scientific research from
MSD KK.
第一作者机构：[1]Department of Cardiology, Fourth Hospital of Hebei Medical University, Shijiazhuang, China
通讯作者：
通讯机构：[3]Division of Clinical Nutrition, Faculty of Home Economics, Kyoritsu Women’s University, Tokyo, Japan[*1]Division of Clinical Nutrition, Kyoritsu Women’s University, 2-2-1 Hitotsubashi, Chiyoda, Tokyo 101-8437, Japan.
推荐引用方式(GB/T 7714)：
Wu Yaqiong,Nakagawa Suguru,Takahashi Hidenori,et al.The angiotensin II receptor antagonist, losartan, enhances regulator of G protein signaling 2 mRNA expression in vascular smooth muscle cells of Wistar rats[J].HYPERTENSION RESEARCH.2016,39(5):295-301.doi:10.1038/hr.2015.154.
APA：
Wu, Yaqiong,Nakagawa, Suguru,Takahashi, Hidenori,Kawabata, Yukari,Suzuki, Etsu&Uehara, Yoshio.(2016).The angiotensin II receptor antagonist, losartan, enhances regulator of G protein signaling 2 mRNA expression in vascular smooth muscle cells of Wistar rats.HYPERTENSION RESEARCH,39,(5)
MLA：
Wu, Yaqiong,et al."The angiotensin II receptor antagonist, losartan, enhances regulator of G protein signaling 2 mRNA expression in vascular smooth muscle cells of Wistar rats".HYPERTENSION RESEARCH 39..5(2016):295-301
