Peroxisome proliferator-activated receptor γ regulates angiotensin II-stimulated phosphatidylinositol 3-kinase and mitogen-activated protein kinase in blood vessels in vivo

被引:49
作者
Benkirane, K [1 ]
Viel, ÉC [1 ]
Amiri, F [1 ]
Schiffrin, EL [1 ]
机构
[1] Clin Res Inst Montreal, Multidisciplinary Res Grp Hypertens, Montreal, PQ H2W 1R7, Canada
关键词
aorta; mesenteric arteries; hypertension; experimental; signal transduction; phosphatases;
D O I
10.1161/01.HYP.0000196728.05488.c3
中图分类号
R6 [外科学];
学科分类号
1002 ; 100210 ;
摘要
Angiotensin (Ang) II is implicated in hypertension, vascular remodeling, and insulin resistance. Peroxisome proliferator-activated receptor (PPAR) gamma activators increase insulin sensitivity and improve Ang II-induced vascular remodeling. We evaluated the effects of the PPAR-gamma activator rosiglitazone on Ang II signaling in aorta and mesenteric arteries. Rats received Ang II by subcutaneous infusion and/or rosiglitazone per os for 7 days. Blood pressure rise in Ang II-infused rats was attenuated by rosiglitazone. Ang II significantly increased Ang II type 1 receptor expression in the mesenteric arteries (P<0.001), whereas that of the aorta was decreased (P<0.05), changes which were reversed by rosiglitazone. Akt activity was increased by Ang II and returned to basal levels under rosiglitazone in both vascular beds. However, Ang II-induced extracellular signal-regulated kinase 1/2 activity increased in aorta but not in mesenteric vessels (P<0.001), where 4E-binding protein 1 activity was significantly increased by Ang II and inhibited by PPAR-gamma activation. In response to Ang II, Src homology (SH)2-containing inositol phosphatase 2 activity was increased (P<0.05) in both vascular beds. In conclusion, PPAR-gamma activator rosiglitazone attenuated Ang II-induced blood pressure elevation and intracellular signaling on aorta and mesenteric vessels. There was differential inhibition of Ang II type 1 receptor receptors/phosphatidylinositol 3-kinase/Akt and extracellular signal-regulated kinase 1/2 in both vessels. Effects of PPAR-gamma activators on these pathways could contribute to regression of vascular remodeling in models of hypertension and diabetes and, accordingly, in hypertensive diabetic patients.
引用
收藏
页码:102 / 108
页数:7
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