This Article Full Text Full Text (PDF) Data Supplement All Versions of this Article: 40/5/660    most recent 01.HYP.0000035397.73223.CEv1 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 Keys, J. R. Articles by Eckhart, A. D. Search for Related Content PubMed PubMed Citation Articles by Keys, J. R. Articles by Eckhart, A. D. Related Collections Cell signalling/signal transduction Genetically altered mice Heart failure - basic studies Hypertension - basic studies Other Vascular biology

(Hypertension. 2002;40:660.)
© 2002 American Heart Association, Inc.

Scientific Contributions

Gq-Coupled Receptor Agonists Mediate Cardiac Hypertrophy Via the Vasculature

From the Department of Surgery, Duke University Medical Center, Durham, NC.

Correspondence to Andrea D. Eckhart, PhD, Department of Surgery, Duke University Medical Center, Box 2606, Room 472A MSRB, Durham, NC 27710. E-mail andrea.eckhart{at}duke.edu

The Gq-coupled receptor-signaling pathway has been implicated in the cardiac hypertrophic response to stress, but little is actually known about the contributions of Gq signaling in either the heart or the vasculature. Therefore, we developed a line of transgenic mice that express a peptide inhibitor of Gq (GqI) in vascular smooth muscle to determine if vascular Gq signaling was important in the cardiac hypertrophic response. After chronic administration of the Gq agonists phenylephrine, serotonin, and angiotensin II, we observed an attenuation of mean arterial blood pressure and an inhibition of cardiac hypertrophy in the transgenic mice with vascular-specific GqI expression. In contrast, cardiac GqI peptide expression did not attenuate the hypertension or the cardiac hypertrophy. Importantly, all mice were capable of cardiac hypertrophy, because direct ß-adrenergic receptor stimulation induced a similar level of hypertrophy in both lines of transgenic mice. This clearly suggests that after chronic Gq-coupled receptor agonist administration, it is the hypertensive state induced by vascular Gq activation that mediates remodeling of the heart, rather than direct stimulation of cardiac Gq-coupled receptors. Thus, the contribution of vascular Gq-coupled signaling to the development of cardiac hypertrophy is significant and suggests that expression of the GqI peptide is a novel therapeutic strategy to lower Gq-mediated hypertension and cardiac hypertrophy.

Key Words: hypertrophy • hypertension, experimental • mice, transgenic • vasculature • receptors, adrenergic

This article has been cited by other articles:

				C. Villeneuve, A. Caudrillier, C. Ordener, N. Pizzinat, A. Parini, and J. Mialet-Perez Dose-dependent activation of distinct hypertrophic pathways by serotonin in cardiac cells Am J Physiol Heart Circ Physiol, August 1, 2009; 297(2): H821 - H828. [Abstract] [Full Text] [PDF]

				A. J. Kimple, M. Soundararajan, S. Q. Hutsell, A. K. Roos, D. J. Urban, V. Setola, B. R. S. Temple, B. L. Roth, S. Knapp, F. S. Willard, et al. Structural Determinants of G-protein {alpha} Subunit Selectivity by Regulator of G-protein Signaling 2 (RGS2) J. Biol. Chem., July 17, 2009; 284(29): 19402 - 19411. [Abstract] [Full Text] [PDF]

				H. I. Cohn, D. M. Harris, S. Pesant, M. Pfeiffer, R.-H. Zhou, W. J. Koch, G. W. Dorn 2nd, and A. D. Eckhart Inhibition of vascular smooth muscle G protein-coupled receptor kinase 2 enhances {alpha}1D-adrenergic receptor constriction Am J Physiol Heart Circ Physiol, October 1, 2008; 295(4): H1695 - H1704. [Abstract] [Full Text] [PDF]

				H. Ohtsu, S. Higuchi, H. Shirai, K. Eguchi, H. Suzuki, A. Hinoki, E. Brailoiu, A. D. Eckhart, G. D. Frank, and S. Eguchi Central Role of Gq in the Hypertrophic Signal Transduction of Angiotensin II in Vascular Smooth Muscle Cells Endocrinology, July 1, 2008; 149(7): 3569 - 3575. [Abstract] [Full Text] [PDF]

				T. Niizeki, Y. Takeishi, T. Kitahara, T. Arimoto, M. Ishino, O. Bilim, S. Suzuki, T. Sasaki, O. Nakajima, R. A. Walsh, et al. Diacylglycerol kinase-{varepsilon} restores cardiac dysfunction under chronic pressure overload: a new specific regulator of G{alpha}q signaling cascade Am J Physiol Heart Circ Physiol, July 1, 2008; 295(1): H245 - H255. [Abstract] [Full Text] [PDF]

				L. E. Vinge, T. G. von Lueder, E. Aasum, E. Qvigstad, J. A. Gravning, O.-J. How, T. Edvardsen, R. Bjornerheim, M. S. Ahmed, B. W. Mikkelsen, et al. Cardiac-restricted Expression of the Carboxyl-terminal Fragment of GRK3 Uncovers Distinct Functions of GRK3 in Regulation of Cardiac Contractility and Growth: GRK3 CONTROLS CARDIAC {alpha}1-ADRENERGIC RECEPTOR RESPONSIVENESS J. Biol. Chem., April 18, 2008; 283(16): 10601 - 10610. [Abstract] [Full Text] [PDF]

				B. R. DeGeorge Jr, E. Gao, M. Boucher, L. E. Vinge, J. S. Martini, P. W. Raake, J. K. Chuprun, D. M. Harris, G. W. Kim, S. Soltys, et al. Targeted Inhibition of Cardiomyocyte Gi Signaling Enhances Susceptibility to Apoptotic Cell Death in Response to Ischemic Stress Circulation, March 18, 2008; 117(11): 1378 - 1387. [Abstract] [Full Text] [PDF]

				D. P. Morris, B. Lei, Y.-X. Wu, G. A. Michelotti, and D. A. Schwinn The {alpha}1a-Adrenergic Receptor Occupies Membrane Rafts with Its G Protein Effectors but Internalizes via Clathrin-coated Pits J. Biol. Chem., February 1, 2008; 283(5): 2973 - 2985. [Abstract] [Full Text] [PDF]

				E. A. Woodcock, X.-J. Du, M. E. Reichelt, and R. M. Graham Cardiac {alpha}1-adrenergic drive in pathological remodelling Cardiovasc Res, February 1, 2008; 77(3): 452 - 462. [Abstract] [Full Text] [PDF]

				D. M. Harris, H. I. Cohn, S. Pesant, R.-H. Zhou, and A. D. Eckhart Vascular smooth muscle Gq signaling is involved in high blood pressure in both induced renal and genetic vascular smooth muscle-derived models of hypertension Am J Physiol Heart Circ Physiol, November 1, 2007; 293(5): H3072 - H3079. [Abstract] [Full Text] [PDF]

				B. E. Isakson, S. I. Ramos, and B. R. Duling Ca2+ and Inositol 1,4,5-Trisphosphate-Mediated Signaling Across the Myoendothelial Junction Circ. Res., February 2, 2007; 100(2): 246 - 254. [Abstract] [Full Text] [PDF]

				Y. Li, S. Hashim, and M. B. Anand-Srivastava Intracellular peptides of natriuretic peptide receptor-C inhibit vascular hypertrophy via Gq{alpha}/MAP kinase signaling pathways Cardiovasc Res, December 1, 2006; 72(3): 464 - 472. [Abstract] [Full Text] [PDF]

				L. Hunyady and K. J. Catt Pleiotropic AT1 Receptor Signaling Pathways Mediating Physiological and Pathogenic Actions of Angiotensin II Mol. Endocrinol., May 1, 2006; 20(5): 953 - 970. [Abstract] [Full Text] [PDF]

				L. Wang, T. A. Fields, K. Pazmino, Q. Dai, J. L. Burchette, D. N. Howell, T. M. Coffman, and R. F. Spurney Activation of G{alpha}q-Coupled Signaling Pathways in Glomerular Podocytes Promotes Renal Injury J. Am. Soc. Nephrol., December 1, 2005; 16(12): 3611 - 3622. [Abstract] [Full Text] [PDF]

				N. Wettschureck and S. Offermanns Mammalian G Proteins and Their Cell Type Specific Functions Physiol Rev, October 1, 2005; 85(4): 1159 - 1204. [Abstract] [Full Text] [PDF]

				J. R. Keys, R.-H. Zhou, D. M. Harris, C. A. Druckman, and A. D. Eckhart Vascular Smooth Muscle Overexpression of G Protein-Coupled Receptor Kinase 5 Elevates Blood Pressure, Which Segregates With Sex and Is Dependent on Gi-Mediated Signaling Circulation, August 23, 2005; 112(8): 1145 - 1153. [Abstract] [Full Text] [PDF]

				J.R. Keys and W.J. Koch The Adrenergic Pathway and Heart Failure Recent Prog. Horm. Res., January 1, 2004; 59(1): 13 - 30. [Abstract] [Full Text]

				J. R. Keys, E. A. Greene, C. J. Cooper, S. V. Naga Prasad, H. A. Rockman, and W. J. Koch Cardiac hypertrophy and altered {beta}-adrenergic signaling in transgenic mice that express the amino terminus of {beta}-ARK1 Am J Physiol Heart Circ Physiol, November 1, 2003; 285(5): H2201 - H2211. [Abstract] [Full Text] [PDF]