| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Internal Medicine, UTMB, Galveston, Texas, United States
2 Biochemistry and Molecular Biology, UTMB, Galveston, Texas, United States
* To whom correspondence should be addressed. E-mail: yobirnba{at}utmb.edu.
Objectives: We assessed whether pioglitazone (PIO) limits infarct size (IS); and whether this protective effect is due to nitric-oxide-synthase (NOS) and/or prostaglandin production, as was shown for atorvastatin (ATV). Whether PIO and ATV have synergistic effects on myocardial protection. Methods: Sprague-Dawley rats received oral ATV (10mg/kg/d), PIO (10mg/kg/d), their combination (PIO&ATV) or sham for 3 days. Additional rats received PIO and SC58125 [a cycloxygenase-2 (COX2) inhibitor] or SC560 (a cycloxygenase-1 inhibitor) 15min before ischemia. Rats underwent 30 min myocardial ischemia and 4h reperfusion, or hearts were harvested for analysis. Results: Infarct size (IS) in the PIO group [13.1% (4.5%) of the area at risk] and in the ATV group [12.4% (3.7%)] was smaller than in the sham group [29.7% (7.4%)]. IS in the PIO&ATV group [5.6% (3.1%)] was smaller than in all other groups (p<0.001 vs. each group). The protective effect of PIO was abrogated by SC58125 [IS 22.7% (3.5%)], but not by SC560 [IS 9.5% (0.8%); p=0.004]. PIO, ATV and PIO&ATV increased the expression and activity of cytosolic-phospholipase-A2 (cPLA2) and COX2. ATV increased phosphorylated-Akt, phosphorylated-endothelial-NOS (P-eNOS), inducible-NOS (iNOS) and COX2 levels. PIO caused an insignificant increase in myocardial levels of phosphorylated-protein-kinase-Akt (P-Akt), but did not significantly change P-eNOS, and iNOS expression. Conclusions: the IS-limiting effects of PIO and ATV involve prostaglandin production by COX2. However, the upstream steps differ. ATV induced eNOS phosphorylation, and iNOS, cPLA2 and COX2 expression, whereas PIO induced mainly the expression and activity of cPLA2. The effects of PIO and ATV were additive.
This article has been cited by other articles:
|
|
 |
|
  M.-H. Huang, V. Nguyen, Y. Wu, S. Rastogi, C. Y. Lui, Y. Birnbaum, H.-Q. Wang, D. L. Ware, M. Chauhan, N. Garg, et al. Reducing ischaemia/reperfusion injury through {delta}-opioid-regulated intrinsic cardiac adrenergic cells: adrenopeptidergic co-signalling Cardiovasc Res, December 1, 2009; 84(3): 452 - 460. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Yasuda, H. Kobayashi, M. Iwasa, I. Kawamura, S. Sumi, B. Narentuoya, T. Yamaki, H. Ushikoshi, K. Nishigaki, K. Nagashima, et al. Antidiabetic drug pioglitazone protects the heart via activation of PPAR-{gamma} receptors, PI3-kinase, Akt, and eNOS pathway in a rabbit model of myocardial infarction Am J Physiol Heart Circ Physiol, May 1, 2009; 296(5): H1558 - H1565. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Ye, Y. Lin, S. Manickavasagam, J. R. Perez-Polo, B. C. Tieu, and Y. Birnbaum Pioglitazone protects the myocardium against ischemia-reperfusion injury in eNOS and iNOS knockout mice Am J Physiol Heart Circ Physiol, December 1, 2008; 295(6): H2436 - H2446. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Gao, W. Wang, and I. H. Zucker Simvastatin Inhibits Central Sympathetic Outflow in Heart Failure by a Nitric-Oxide Synthase Mechanism J. Pharmacol. Exp. Ther., July 1, 2008; 326(1): 278 - 285. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Ye, J. D. Martinez, R. J. Perez-Polo, Y. Lin, B. F. Uretsky, and Y. Birnbaum The role of eNOS, iNOS, and NF-{kappa}B in upregulation and activation of cyclooxygenase-2 and infarct size reduction by atorvastatin Am J Physiol Heart Circ Physiol, July 1, 2008; 295(1): H343 - H351. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y.-J. Yang, H.-Y. Qian, J. Huang, Y.-J. Geng, R.-L. Gao, K.-F. Dou, G.-S. Yang, J.-J. Li, R. Shen, Z.-X. He, et al. Atorvastatin treatment improves survival and effects of implanted mesenchymal stem cells in post-infarct swine hearts Eur. Heart J., June 2, 2008; 29(12): 1578 - 1590. [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]
|
|
|
|
 |
|
 E. Erdmann Review: Statin plus thiazolidinedione use in patients with diabetes at high cardiovascular risk The British Journal of Diabetes & Vascular Disease, September 1, 2007; 7(5): 211 - 216. [Abstract] [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]
|
|
|
|
|
|
M.-H. Huang, H.-Q. Wang, W. R. Roeske, Y. Birnbaum, Y. Wu, N.-P. Yang, Y. Lin, Y. Ye, D. J. McAdoo, M. G. Hughes, et al. Mediating {delta}-opioid-initiated heart protection via the beta2-adrenergic receptor: role of the intrinsic cardiac adrenergic cell Am J Physiol Heart Circ Physiol, July 1, 2007; 293(1): H376 - H384. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Ye, Y. Lin, R. Perez-Polo, M.-H. Huang, M. G. Hughes, D. J. McAdoo, S. Manickavasagam, B. F. Uretsky, and Y. Birnbaum Enhanced cardioprotection against ischemia-reperfusion injury with a dipyridamole and low-dose atorvastatin combination Am J Physiol Heart Circ Physiol, July 1, 2007; 293(1): H813 - H818. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Salinas, U. C. Rangasetty, B. F. Uretsky, and Y. Birnbaum The Cycloxygenase 2 (COX-2) Story: It's Time to Explain, Not Inflame Journal of Cardiovascular Pharmacology and Therapeutics, June 1, 2007; 12(2): 98 - 111. [Abstract] [PDF]
|
|
|
|
|
|
Y. Birnbaum, Y. Lin, Y. Ye, J. D. Martinez, M.-H. Huang, C. Y. Lui, J. R Perez-Polo, and B. F. Uretsky Aspirin before reperfusion blunts the infarct size limiting effect of atorvastatin Am J Physiol Heart Circ Physiol, June 1, 2007; 292(6): H2891 - H2897. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| Visit Other APS Journals Online |
