| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Cardiovascular Research Center and Department of Physiology (H.O., S.H., H.Sh., K.E., H.Su., A.H., S.E.) and Department of Pharmacology (E.B.), Temple University School of Medicine, Philadelphia, Pennsylvania 19140; Center for Translational Medicine (A.D.E.), Thomas Jefferson University, Philadelphia, Pennsylvania 19107; and Department of Biochemistry (G.D.F.), Vanderbilt University School of Medicine, Nashville, Tennessee 37232
Address all correspondence and requests for reprints to: Satoru Eguchi, M.D., Ph.D., F.A.H.A., Cardiovascular Research Center and Department of Physiology, Temple University School of Medicine, 3420 North Broad Street, Philadelphia, Pennsylvania 19140. E-mail: seguchi{at}temple.edu.
The angiotensin II (AngII) type 1 receptor (AT1) plays a critical role in hypertrophy of vascular smooth muscle cells (VSMCs). Although it is well known that Gq is the major G protein activated by the AT1 receptor, the requirement of Gq for AngII-induced VSMC hypertrophy remains unclear. By using cultured VSMCs, this study examined the requirement of Gq for the epidermal growth factor receptor (EGFR) pathway, the Rho-kinase (ROCK) pathway, and subsequent hypertrophy. AngII-induced intracellular Ca2+ elevation was completely inhibited by a pharmacological Gq inhibitor as well as by adenovirus encoding a Gq inhibitory minigene. AngII (100nM)-induced EGFR transactivation was almost completely inhibited by these inhibitors, whereas these inhibitors only partially inhibited AngII (100nM)-induced phosphorylation of a ROCK substrate, myosin phosphatase target subunit-1. Stimulation of VSMCs with AngII resulted in an increase of cellular protein and cell volume but not in cell number. The Gq inhibitors completely blocked these hypertrophic responses, whereas a G protein-independent AT1 agonist did not stimulate these hypertrophic responses. In conclusion, Gq appears to play a major role in the EGFR pathway, leading to vascular hypertrophy induced by AngII. Vascular Gq seems to be a critical target of intervention against cardiovascular diseases associated with the enhanced renin-angiotensin system.
This article has been cited by other articles:
![]() |
J. Bregeon, G. Loirand, P. Pacaud, and M. Rolli-Derkinderen Angiotensin II induces RhoA activation through SHP2-dependent dephosphorylation of the RhoGAP p190A in vascular smooth muscle cells Am J Physiol Cell Physiol, November 1, 2009; 297(5): C1062 - C1070. [Abstract] [Full Text] [PDF] |
||||
![]() |
K. Kimura and S. Eguchi Angiotensin II type-1 receptor regulates RhoA and Rho-kinase/ROCK activation via multiple mechanisms. Focus on "Angiotensin II induces RhoA activation through SHP2-dependent dephosphorylation of the RhoGAP p190A in vascular smooth muscle cells" Am J Physiol Cell Physiol, November 1, 2009; 297(5): C1059 - C1061. [Full Text] [PDF] |
||||
![]() |
H. Suzuki, K. Kimura, H. Shirai, K. Eguchi, S. Higuchi, A. Hinoki, K. Ishimaru, E. Brailoiu, D. N. Dhanasekaran, L. N. Stemmle, et al. Endothelial Nitric Oxide Synthase Inhibits G12/13 and Rho-Kinase Activated by the Angiotensin II Type-1 Receptor: Implication in Vascular Migration Arterioscler Thromb Vasc Biol, February 1, 2009; 29(2): 217 - 224. [Abstract] [Full Text] [PDF] |
||||
![]() |
H. Suzuki, E. D. Motley, K. Eguchi, A. Hinoki, H. Shirai, V. Watts, L. N. Stemmle, T. A. Fields, and S. Eguchi Distinct Roles of Protease-Activated Receptors in Signal Transduction Regulation of Endothelial Nitric Oxide Synthase Hypertension, February 1, 2009; 53(2): 182 - 188. [Abstract] [Full Text] [PDF] |
||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Endocrinology | Endocrine Reviews | J. Clin. End. & Metab. |
| Molecular Endocrinology | Recent Prog. Horm. Res. | All Endocrine Journals |