Skip Navigation



Cardiovascular Research Advance Access [Accepted Manuscript] published online on January 9, 2009
Cardiovascular Research, doi:10.1093/cvr/cvp005
This Article
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
82/1/100    most recent
cvp005v2
cvp005v1
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 Schmechel, A.
Right arrow Articles by Eschenhagen, T.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Schmechel, A.
Right arrow Articles by Eschenhagen, T.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2009. For permissions please email: journals.permissions@oxfordjournals.org.

Treatment with atorvastatin partially protects the rat heart from harmful catecholamine effects

Ariane Schmechel, PhD1, Michael Grimm, MD1, Ali El-Armouche, MD1, Grit Höppner1, Alexander P. Schwoerer, MD2, Heimo Ehmke, MD2 and Thomas Eschenhagen, MD1

1 Department of Experimental and Clinical Pharmacology
2 Department of Vegetative Physiology and Pathophysiology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

Address correspondence to: Thomas Eschenhagen, Department of Experimental and Clinical Pharmacology, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246 Hamburg, Germany. Phone: 49-40-42803-2180; Fax: 49-40-42803-4876; E-mail: t.eschenhagen{at}uke.uni-hamburg.de.

Aims: Atorvastatin blunts the response of cardiomyocytes to catecholamines by reducing isoprenylation of G{gamma} subunits. We examined whether atorvastatin exerts similar effects in vivo and protects the rat heart from harmful effects of catecholamines.

Methods: Rats were treated with atorvastatin (1 or 10 mg/kg x d) or H2O for 14 days per gavage. All 3 animal groups were subjected to restraint stress on day 10 and to infusions of isoprenaline (ISO; 1 mg/kg x d) or NaCl via minipumps for the last 4 days. Heart rate was measured by telemetry, left ventricular atrial natriuretic peptide (ANP) transcript levels by RT-PCR and left atrial contractile function in organ baths.

Results: Heart rate was similar in all 6 study groups. In animals pretreated with water, infusion of ISO induced an increase in heart-to-body weight ratio (HW/BW) by ~20%, an increase in atrial natriuretic peptide (ANP) mRNA by ~350%, and a reduction in the inotropic effect of isoprenaline in left atrium by ~50%. In animals pre-treated with high-dose atorvastatin the effects of ISO on HW/BW, ANP and left atrial force were ~40%, 50% and 40% smaller, respectively. Low dose atorvastatin had similar, albeit smaller effects. Atorvastatin-treatment of NaCl-infused rats had only marginal effects. In cardiac homogenates from atorvastatin-treated rats (both NaCl- and ISO-infused), G{gamma} and G{alpha} were partially translocated from the membrane to the cytosol.

Conclusions: In the rat heart, treatment with atorvastatin results in translocation of cardiac membrane G{gamma} and G{alpha} to the cytosol. This mechanism might contribute to protecting the heart from harm induced by chronic isoprenaline infusion without affecting heart rate.

Time for primary review: 24 Days


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




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.