JPET

Home Help [Feedback] [For Subscribers] [Archive] [Search] --
QUICK SEARCH:   [advanced]


     

Journal of Pharmacology And Experimental Therapeutics Fast Forward
First published on August 25, 2005; DOI: 10.1124/jpet.105.090993

This Article
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
jpet.105.090993v1
315/3/1020    most recent
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Services
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 Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Johns, D. G.
Right arrow Articles by Macphee, C. H.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Johns, D. G.
Right arrow Articles by Macphee, C. H.
Right arrowPubmed/NCBI databases
*Compound via MeSH
*Substance via MeSH
Medline Plus Health Information
*Cardiomyopathy
*Heart Attack


Received for publication June 15, 2005.
Revised August 11, 2005.
Accepted for publication August 24, 2005.

Rosiglitazone protects against ischemia/reperfusion-induced leukocyte adhesion in the Zucker diabetic fatty rat

Douglas G. Johns 1*, Zhaohui Ao 1, Marianne Eybye 1, Alan Olzinski 1, Melissa Costell 1, Susan Gruver 1, Stephen A. Smith 1, Stephen A. Douglas 1, Colin H. Macphee 1

1 GlaxoSmithKline

* Address correspondence to: E-mail: douglas.g.johns{at}gsk.com

Abstract

Increased susceptibility to atherosclerosis increases the risk of mortality in type 2 diabetic patients. Leukocyte adhesion to the endothelium is a critical step in atherogenesis. In addition to its insulin-sensitizing effects, rosiglitazone (RSG) possesses anti-inflammatory properties. The effects of RSG, however, on the initial phase of leukocyte recruitment (rolling, adhesion) have not been studied in vivo. This study tested the hypothesis that RSG treatment of Zucker diabetic fatty (ZDF) rats inhibits ischemia-reperfusion-induced leukocyte adhesion to the endothelium. Male ZDF rats (16 wk) were treated with RSG (3mg/kg/d, p.o.) 7d before experimentation. Leukocyte-endothelial interactions in cremaster venules were recorded using intravital microscopy prior to 30min of ischemia and during a 90min reperfusion period. While blood pressure, plasma glucose and insulin were not different between treatment groups, RSG treatment was associated with reduced leukocyte rolling and inhibition of leukocyte adhesion throughout the reperfusion period (P<0.01). Cremaster mRNA expression of VCAM-1 was reduced by 35% in RSG-treated animals (P<0.01), whereas P- and E-selectin and ICAM-1 were unchanged. Immunostaining for P-selectin, E-selectin, and VCAM-1 was reduced by 21%, 61%, and 50%, respectively (for all, P<0.05) in RSG-treated animals. Inhibition of ischemia/reperfusion-induced leukocyte adhesion might contribute to the utility of RSG as a therapy for atherosclerosis.


Key words: Intravital microscopy, Ischemia-reperfusion, PPAR-gamma agonists, Rosiglitazone, Zucker diabetic fatty rat, leukocyte


This article has been cited by other articles:


Home page
 Physiol. Rev.Home page
E. D. Abel, S. E. Litwin, and G. Sweeney
Cardiac Remodeling in Obesity
Physiol Rev, April 1, 2008; 88(2): 389 - 419.
[Abstract] [Full Text] [PDF]

Home page
 CirculationHome page
S. Boudina and E. D. Abel
Diabetic Cardiomyopathy Revisited
Circulation, June 26, 2007; 115(25): 3213 - 3223.
[Abstract] [Full Text] [PDF]

Home page
 Exp. Biol. Med.Home page
J. D. Knudson, G. M. Dick, and J. D. Tune
Adipokines and Coronary Vasomotor Dysfunction
Experimental Biology and Medicine, June 1, 2007; 232(6): 727 - 736.
[Abstract] [Full Text] [PDF]


Home Help [Feedback] [For Subscribers] [Archive] [Search] --
All ASPET Journals Molecular Pharmacology Pharmacological Reviews
Molecular Interventions Drug Metabolism and Disposition

Copyright © 2005 by the American Society for Pharmacology and Experimental Therapeutics.