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1 Medicine/Division of cardiology, University of Arkansas for Medical Sciences, Little Rock, Arkansas, United States; Medicine/Division of Cardiology, Central Arkansas Veterans Healthcare System, Little Rock, Arkansas, United States
* To whom correspondence should be addressed. E-mail: molavibehzad{at}uams.edu.
Background
Current evidence points to renin-angiotensin system (RAS) as a key mediator in ischemia-reperfusion injury. Rosiglitazone, a peroxisome-proliferator activated receptor-gamma (PPAR-
ligand has recently been shown to confer cardioprotection against ischemia-reperfusion in animal models. We sought to examine the expression of angiotensin II receptors during PPAR-[[gamma]-mediated cardioprotection.
Materials and Methods
Male Sprague-Dawley rats (non-diabetic) were fed either regular rat chow (control diet group, n=9) or rosiglitazone-rich diet (rosiglitazone-rich diet group, n=9) and were subjected to one hour of myocardial ischemia followed by one hour of reperfusion. A third group of rats had only thoracotomy and pericardiotomy and served as a sham control group (n=9). Hemodynamics, infarct size and expression of Ang II type 1 and type 2 receptors (AT1 and AT2) were measured in all groups.
Results
There was a 58% reduction of infarct size in the rosiglitazone-rich diet group (P<0.01 vs. control diet group). Increased myocardial expression of AT1 receptors in the ischemic-reperfused myocardium was attenuated in the rosiglitazone-rich diet group (P<0.05 vs. control diet group). Importantly, myocardial AT2 mRNA and protein expression were significantly increased (by > 100 folds) in the rosiglitazone-rich diet group (P<0.05). These changes were accompanied by inhibition of P42/44 MAPK in the rosiglitazone-rich diet group, while the Akt1 expression, believed to mediate insulin sensitization, remained similar in all three groups.
Conclusion
The cardioprotective effects of rosiglitazone against myocardial ischemia-reperfusion injury are independent of its insulin-sensitizing properties and are associated with significant over-expression of AT2 receptors along with inhibition of P42/44 MAPK.
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