Published in:
01-08-2009
Pharmacological Preconditioning in Type 2 Diabetic Rat Hearts: The Roles of Mitochondrial ATP-Sensitive Potassium Channels and the Phosphatidylinositol 3-Kinase-Akt Pathway
Published in: Cardiovascular Drugs and Therapy | Issue 4/2009
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Purpose
The authors examined whether olprinone, a phosphodiesterase type 3 inhibitor, or isoflurane, a volatile anesthetic, could protect the heart against myocardial infarction in type 2 diabetic rats and whether the underlying mechanisms involve protein kinase C (PKC), mitochondrial ATP-sensitive potassium (m-KATP) channels, or the phosphatidylinositol 3-kinase (PI3K)-Akt pathway.
Methods
All rats underwent 30 min of coronary artery occlusion followed by 2 h of reperfusion. Wistar rats received isoflurane or olprinone before ischemia with or without the PKC inhibitor chelerythrine (CHE), the m-KATP channel blocker 5-hydroxydecanoic acid (5HD), or the PI3K-Akt inhibitor LY294002 (LY). Goto-Kakizaki (GK) rats were randomly assigned to receive isoflurane or olprinone. In another group, GK rats received LY before the olprinone.
Results
In the Wistar rats, both isoflurane (38 ± 11%) and olprinone (40 ± 11%) reduced infarct size as compared to the control group (59 ± 8%). In the GK rats, olprinone (41 ± 9%) but not isoflurane (53 ± 11%) reduced infarct size as compared to the GK control group (58 ± 14%). The beneficial effects of olprinone were blocked by LY (58 ± 14%). In the Wistar rats, CHE, 5HD, and LY prevented isoflurane-induced reductions of infarct size. On the other hand, LY but not CHE or 5HD prevented olprinone-induced reductions of infarct size.
Conclusions
Olprinone but not isoflurane protects the heart against myocardial infarction in type 2 diabetic rats. The olprinone-induced cardioprotective effect is mediated by the PI3K-Akt pathway but not PKC or m-KATP channels.