This Article Full Text Full Text (PDF) Data Supplement All Versions of this Article: 47/1/102    most recent 01.HYP.0000196728.05488.c3v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Benkirane, K. Articles by Schiffrin, E. L. Search for Related Content PubMed PubMed Citation Articles by Benkirane, K. Articles by Schiffrin, E. L. Pubmed/NCBI databases Gene GEO Profiles HomoloGene UniGene Compound via MeSH Substance via MeSH Related Collections Cell signalling/signal transduction Smooth muscle proliferation and differentiation Other Vascular biology

(Hypertension. 2006;47:102.)
© 2006 American Heart Association, Inc.

Original Articles

Peroxisome Proliferator–Activated Receptor Regulates Angiotensin II–Stimulated Phosphatidylinositol 3-Kinase and Mitogen-Activated Protein Kinase in Blood Vessels In Vivo

From the Multidisciplinary Research Group on Hypertension, Clinical Research Institute of Montreal, Montreal, Quebec, Canada.

Correspondence to Ernesto L. Schiffrin, Clinical Research Institute of Montreal, 110 Pine Ave West, Montreal, Quebec, Canada H2W 1R7. E-mail ernesto.schiffrin{at}ircm.qc.ca

Angiotensin (Ang) II is implicated in hypertension, vascular remodeling, and insulin resistance. Peroxisome proliferator–activated receptor (PPAR) activators increase insulin sensitivity and improve Ang II–induced vascular remodeling. We evaluated the effects of the PPAR- 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- 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- 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- activators on these pathways could contribute to regression of vascular remodeling in models of hypertension and diabetes and, accordingly, in hypertensive diabetic patients.

Key Words: aorta • mesenteric arteries • hypertension, experimental • signal transduction • phosphatases

This article has been cited by other articles:

				A. Jones, R. Deb, E. Torsney, F. Howe, M. Dunkley, Y. Gnaneswaran, D. Gaze, H. Nasr, I. M. Loftus, M. M. Thompson, et al. Rosiglitazone Reduces the Development and Rupture of Experimental Aortic Aneurysms Circulation, June 23, 2009; 119(24): 3125 - 3132. [Abstract] [Full Text] [PDF]

				L. Chang, L. Villacorta, J. Zhang, M. T. Garcia-Barrio, K. Yang, M. Hamblin, S. E. Whitesall, L. G. D'Alecy, and Y. E. Chen Vascular Smooth Muscle Cell-Selective Peroxisome Proliferator-Activated Receptor-{gamma} Deletion Leads to Hypotension Circulation, April 28, 2009; 119(16): 2161 - 2169. [Abstract] [Full Text] [PDF]

				A. Tawfik, T. Sanders, K. Kahook, S. Akeel, A. Elmarakby, and M. Al-Shabrawey Suppression of Retinal Peroxisome Proliferator-Activated Receptor {gamma} in Experimental Diabetes and Oxygen-Induced Retinopathy: Role of NADPH Oxidase Invest. Ophthalmol. Vis. Sci., February 1, 2009; 50(2): 878 - 884. [Abstract] [Full Text] [PDF]

				F. Scalera, J. Martens-Lobenhoffer, A. Bukowska, U. Lendeckel, M. Tager, and S. M. Bode-Boger Effect of Telmisartan on Nitric Oxide-Asymmetrical Dimethylarginine System: Role of Angiotensin II Type 1 Receptor and Peroxisome Proliferator Activated Receptor {gamma} Signaling During Endothelial Aging Hypertension, March 1, 2008; 51(3): 696 - 703. [Abstract] [Full Text] [PDF]

				D. Seto-Young, D. Avtanski, M. Strizhevsky, G. Parikh, P. Patel, J. Kaplun, K. Holcomb, Z. Rosenwaks, and L. Poretsky Interactions among Peroxisome Proliferator Activated Receptor-{gamma}, Insulin Signaling Pathways, and Steroidogenic Acute Regulatory Protein in Human Ovarian Cells J. Clin. Endocrinol. Metab., June 1, 2007; 92(6): 2232 - 2239. [Abstract] [Full Text] [PDF]