| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, Texas, United States
2 Internal Medicine, University of Texas Medical Branch, Galveston, Texas, United States
3 Neuroscience and Cell Biology, University of Texas Medical Branch, Galveston, Texas, United States
4 Internal Medicine, University of Texas Medical branch, Galveston, Texas, United States
5 Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, Texas, United States; Internal Medicine, University of Texas Medical Branch, Galveston, Texas, United States
* To whom correspondence should be addressed. E-mail: yobirnba{at}utmb.edu.
Objectives: Atorvastatin (ATV) limits infarct size (IS) by activating Akt and ecto-5-nucleotidase, which generates adenosine. Activated Akt and adenosine activate endothelial nitric oxide synthase (eNOS). When given orally, high doses (10mg/kg) are needed to achieve full protection. We determined whether dipyridamole (DIP), by preventing the reuptake of adenosine, has a synergistic effect with ATV in reducing myocardial IS. Methods: Rats received 3-day: 1) water; 2) ATV (2mg/kg/d); 3) DIP (6mg/kg/d); or 4) ATV+DIP. In addition, rats received 3-day 1) aminophylline (AMINO; 10mg/kg/d), or 2) AMINO+ATV+DIP). Rats underwent 30min myocardial ischemia followed by 4h reperfusion (IS protocol), or hearts were explanted for immunoblotting. Results: IS in the controls was 34.0±2.8% of the area at risk. ATV (33.1±2.1%) and DIP (30.5±1.5%) did not affect IS, whereas ATV+DIP reduced IS (12.2±0.5%; p<0.001 versus each of the other groups). There was no difference in IS between the AMINO alone (48.1±0.8%) and the AMINO+ATV+DIP (45.8±2.9%) group (p=0.422), suggesting that AMINO completely blocked the protective effect. Myocardial adenosine level in the controls was 30.6±3.6 pg/µl. ATV (51.0±4.9) and DIP (51.5±6.8) tended to increase adenosine levels, whereas ATV+DIP caused a significant increase in adenosine levels (66.4±3.1 pg/µl; p<0.05 versus the controls and DIP). ATV and DIP alone did not affect myocardial Ser-473 phosphorylated-Akt and Ser-1177 phosphorylated-eNOS levels, whereas ATV+DIP significantly increased them. Conclusions: Low-dose ATV and DIP had synergistic effects in reducing myocardial IS and activation of Akt and eNOS. This combination may have a potential benefit in augmenting the eNOS-mediated pleiotropic effects of statins.
This article has been cited by other articles:
|
|
 |
|
  P. Meijer, W. J.G. Oyen, D. Dekker, P. H.H. van den Broek, C. W. Wouters, O. C. Boerman, G. J. Scheffer, P. Smits, and G. A. Rongen Rosuvastatin Increases Extracellular Adenosine Formation in Humans In Vivo: A New Perspective on Cardiovascular Protection Arterioscler Thromb Vasc Biol, June 1, 2009; 29(6): 963 - 968. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. K. Mohan, M. Khan, S. Wisel, K. Selvendiran, A. Sridhar, C. A. Carnes, B. Bognar, T. Kalai, K. Hideg, and P. Kuppusamy Cardioprotection by HO-4038, a novel verapamil derivative, targeted against ischemia and reperfusion-mediated acute myocardial infarction Am J Physiol Heart Circ Physiol, January 1, 2009; 296(1): H140 - H151. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Matsuhisa, H. Otani, T. Okazaki, K. Yamashita, Y. Akita, D. Sato, A. Moriguchi, H. Imamura, and T. Iwasaka Angiotensin II type 1 receptor blocker preserves tolerance to ischemia-reperfusion injury in Dahl salt-sensitive rat heart Am J Physiol Heart Circ Physiol, June 1, 2008; 294(6): H2473 - H2479. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Birnbaum, Y. Lin, Y. Ye, R. Merla, J. R. Perez-Polo, and B. F. Uretsky Pretreatment With High-Dose Statin, But Not Low-Dose Statin, Ezetimibe, or the Combination of Low-Dose Statin and Ezetimibe, Limits Infarct Size in the Rat Journal of Cardiovascular Pharmacology and Therapeutics, March 1, 2008; 13(1): 72 - 79. [Abstract] [PDF]
|
|
|
|
|
|
H.-H. Kim and J. K. Liao Translational Therapeutics of Dipyridamole Arterioscler Thromb Vasc Biol, March 1, 2008; 28(3): s39 - s42. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Merla, Y. Ye, Y. Lin, S. Manickavasagam, M.-H. Huang, R. J. Perez-Polo, B. F. Uretsky, and Y. Birnbaum The central role of adenosine in statin-induced ERK1/2, Akt, and eNOS phosphorylation Am J Physiol Heart Circ Physiol, September 1, 2007; 293(3): H1918 - H1928. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| Visit Other APS Journals Online |
