Skip Navigation

Cardiovascular Research 2004 63(3):561-572; doi:10.1016/j.cardiores.2004.01.026
© 2004 by European Society of Cardiology
This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow E-letters: Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when E-letters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Petrashevskaya, N. N
Right arrow Articles by Schwartz, A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Petrashevskaya, N. N
Right arrow Articles by Schwartz, A.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Copyright © 2004, European Society of Cardiology

Effects of {alpha}1-adrenergic stimulation on normal and hypertrophied mouse hearts. Relation to caveolin-3 expression

Natalia N Petrashevskaya, Ilona Bodi, Sheryl E Koch, Shahab A Akhter and Arnold Schwartz*

Department of Surgery, Cardiovascular Research Center, Institute of Molecular Pharmacology and Biophysics, University of Cincinnati College of Medicine, 231 Albert Sabin Way, Cincinnati OH 45267-0828, USA

* Corresponding author. Tel.: +1-513-558-2400; fax: +1-513-558-1778. Email address: schwara{at}email.uc.edu

Background: Modulation of the transduction efficiency through G-protein coupled receptors, caused by external stimulation, is essential in designing antihypertrophic treatment strategies in the dysfunctional heart. We compared protein-kinase C (PKC)-dependent regulation of positive inotropic effect via {alpha}1-adrenoreceptor (ADR)/Gq protein in hyperdynamic versus hypertrophied myocardium. Methods: Inotropic (work performing isolated heart) and cellular effects of {alpha}1-adrenoreceptor stimulation were studied in nontransgenic (Ntg) and transgenic (Tg) mice with cardiac specific overexpression of L-type voltage-dependent calcium channels (L-type VDCC). Results: Transgenic hyperdynamic and hypertrophic myocardium (due to overexpression of the L-type VDCC {alpha}1 subunit) were characterized by a lack of positive inotropic effect (PIE) to {alpha}1-ADR stimulation with phenylephrine (PE), as compared to a positive response in Ntg hearts. This was partially restored by PKC inhibition with chelerythrine and staurosporine only at the hyperdynamic stage. The inability of PKC inhibition to increase positive inotropy was associated with markedly decreased cardiac-specific caveolin-3 expression, and no changes in G{alpha}q, PLC-β1, caveolin-1 and {alpha}1-adrenoreceptor expression. Conclusion: In the hyperdynamic myocardium, PKC activation may be one of the switches responsible for an impaired {alpha}1-adrenergic positive inotropic response. In the hypertrophied myocardium, the interruption of the transduction from G{alpha}q-protein coupled receptors to downstream effectors may be due to the down-regulation of caveolin-3 expression.

KEYWORDS Myocardium; Receptors; Adrenergic; Alpha; Calcium; Hypertrophy; Signal transduction

Time for primary review 27 days


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 Circ. Res.Home page
C. D. Wright, Q. Chen, N. L. Baye, Y. Huang, C. L. Healy, S. Kasinathan, and T. D. O'Connell
Nuclear {alpha}1-Adrenergic Receptors Signal Activated ERK Localization to Caveolae in Adult Cardiac Myocytes
Circ. Res., October 24, 2008; 103(9): 992 - 1000.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Heart Circ. Physiol.Home page
G.-Y. Wang, D. T. McCloskey, S. Turcato, P. M. Swigart, P. C. Simpson, and A. J. Baker
Contrasting inotropic responses to {alpha}1-adrenergic receptor stimulation in left versus right ventricular myocardium
Am J Physiol Heart Circ Physiol, October 1, 2006; 291(4): H2013 - H2017.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Heart Circ. Physiol.Home page
H. H. Patel, B. P. Head, H. N. Petersen, I. R. Niesman, D. Huang, G. J. Gross, P. A. Insel, and D. M. Roth
Protection of adult rat cardiac myocytes from ischemic cell death: role of caveolar microdomains and {delta}-opioid receptors
Am J Physiol Heart Circ Physiol, July 1, 2006; 291(1): H344 - H350.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
M. S. George and G. S. Pitt
The real estate of cardiac signaling: Location, location, location
PNAS, May 16, 2006; 103(20): 7535 - 7536.
[Full Text] [PDF]

Home page
 Circ. Res.Home page
D. Urboniene, F. A.L. Dias, J. R. Pena, L. A. Walker, R. J. Solaro, and B. M. Wolska
Expression of Slow Skeletal Troponin I in Adult Mouse Heart Helps to Maintain the Left Ventricular Systolic Function During Respiratory Hypercapnia
Circ. Res., July 8, 2005; 97(1): 70 - 77.
[Abstract] [Full Text] [PDF]

Home page
 Cardiovasc ResHome page
B. R. Rorabaugh, S. A. Ross, R. J. Gaivin, R. S. Papay, D. F. McCune, P. C. Simpson, and D. M. Perez
{alpha}1A- but not {alpha}1B-adrenergic receptors precondition the ischemic heart by a staurosporine-sensitive, chelerythrine-insensitive mechanism
Cardiovasc Res, February 1, 2005; 65(2): 436 - 445.
[Abstract] [Full Text] [PDF]


Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.